Systemic absorption of epinephrine compared between the intranasal and intramuscular routes of administration in healthy adults.

BACKGROUND: Epinephrine 5 mg administered via the intranasal (IN) route was shown to be bioequivalent to epinephrine 0.3 mg administered via the intramuscular (IM) route in our preliminary study. OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of IN and IM epinephrine absorption in a larger group of healthy adults (n = 12). METHODS: Each subject was administered IN saline, IN epinephrine (5 mg), and IM epinephrine (0.3 mg) on 3 separate days. Plasma epinephrine levels were determined using liquid chromatography-tandem mass spectrometry. RESULTS: IN epinephrine administration showed significant systemic absorption compared to IN saline control with the areas under the curve (AUC0-180 min) of 4.4 (4.9) ± 4.0 and 0.2 (0.5) ± 0.3 ng.min/mL, respectively; the values are mean (median) ± standard deviation. IN epinephrine absorption was about 0.5-fold that of IM epinephrine (AUC0-180 min 10.0 (9.2) ± 8.6 ng.min/mL), but the difference was not statistically significant (p = 0.16). The mean peak epinephrine concentration and the time to reach it were also not significantly different between the IN and IM routes. The corresponding values were 120 pg/mL and 41 min for IN, and 209 pg/mL and 41 min for IM, respectively. CONCLUSIONS: The systemic absorption of IN epinephrine 5 mg was significantly different from the control IN saline and about 0.5-fold that of IM epinephrine 0.3 mg. Although epinephrine administration via the less invasive IN route is safe and feasible, further investigations are necessary to achieve an adequate and consistent systemic absorption comparable to that of the conventional IM injection.

Bioequivalence Study of 100-mg Cilostazol Tablets in Healthy Thai Adult Volunteers.

BACKGROUND: Cilostazol is a vasodilator with anticoagulant effect for treatment of peripheral vascular disease. Cilostazol 100-mg tablet was shown to increase walking distance in this patient population. OBJECTIVE: The aim of this study was to investigate and compare the pharmacokinetic profiles and safety of Bestazol 100-mg tablet (Berlin Pharmaceutical Industry Co Ltd, Bangkok, Thailand), which is a generic formulation of cilostazol, with the original brand Pletaal 100-mg tablet (Korea Otsuka Pharmaceutical Co Ltd, Seoul, South Korea) in healthy Thai adult volunteers. METHODS: The pharmacokinetic profiles of Bestazol (test) and Pletaal (reference) 100-mg tablets were compared in a single-dose, open-label, 2-treatment, 2-period, 2-sequence, randomized crossover study in healthy Thai adult volunteers. This study was conducted at the Siriraj Clinical Research Center, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Each volunteer was initially treated according to either the test-reference or the reference-test sequence, after which each volunteer was switched to the other study sequence after a 2-week washout period. Pharmacokinetic analysis was performed using log-transformed ratios for Cmax, AUC0-last, AUC0-∞, Tmax, t1/2, and λZ for both cilostazol and 3,4-dehydro-cilostazol (its active metabolite) with 90% CI. Physical examination, clinical laboratory data, vital signs, and adverse events were assessed in all participants. FINDINGS: A total of 28 volunteers were included in the final analysis. The ratios of the geometric mean and the 90% CI compared test to reference of cilostazol formulations and were 101.86% (90% CI, 91.88%-112.92%), 107.78% (90% CI, 99.67%-116.56%), and 110.46% (90% CI, 102.68%-118.82%) for Cmax, AUC0-last, and AUC0-∞, respectively. The ratios of the geometric mean and the 90% CI compared test to reference of 3,4-dehydro-cilostazol and were 106.72% (95% CI, 95.31%-119.50%), 110.54% (95% CI, 101.92%-119.89%), and 107.37% (95% CI, 96.74%-119.16%) for Cmax, AUC0-last, and AUC0-∞, respectively. No significant difference was observed between formulations for Tmax. The most common adverse event was headache (51.85%), with no significant difference in incidence between the test and reference groups. No serious adverse events related to the studied drugs were reported. The findings of this study indicate these 2 cilostazol tablet formulations to be bioequivalent. CONCLUSIONS: Bestazol 100-mg tablet was bioequivalent to Pletaal 100-mg tablet. Thus, the formulations can be used interchangeably in clinical practice.

Hypovitaminosis D in healthy children in Central Thailand: prevalence and risk factors.

BACKGROUND: There are limited data regarding the prevalence and risk factors relating to hypovitaminosis D in children of Thailand, a tropical country with abundant sunlight. The objective of this study was to assess the prevalence of hypovitaminosis D and examine factors associated with hypovitaminosis D in school-aged children in Bangkok, Thailand - a centrally located capital city. METHODS: This cross-sectional study evaluated 159 healthy children (33.3% boys and 66.7% girls), aged 6 to 12 years, in Bangkok, Thailand (located at 13.45°N). Fasting plasma samples were examined for total 25-hydroxyvitamin D [25(OH)D] using electrochemiluminescence immunoassay. Demographic characteristics (age, sex, household income), past medical history (birth weight, allergic diseases, hospitalization), amount of sun exposure, anthropometric data, and selected biochemical tests were used to investigate for factors associated with hypovitaminosis D. RESULTS: Overall, the mean ± SD level of plasma 25(OH)D was 64.0 ± 15.1 nmol/L. Hypovitaminosis D (< 75 nmol/L) was presented in 79.2% of subjects. Of these, the prevalence of vitamin D insufficiency and vitamin D deficiency were 59.7% and 19.5%, respectively. In univariate analysis, children with hypovitaminosis D (< 75 nmol/L) had a higher mean body mass index (BMI) percentile than the vitamin D-sufficient group (56.7 ± 33.9 vs. 42.6 ± 36.0; P-value = 0.04). Plasma PTH levels in the children with hypovitaminosis D were significantly higher than in the children with normal levels of vitamin D (4.34 ± 1.38 vs 3.78 ± 1.25 pmol/L; P-value = 0.04). In multivariate analysis, high BMI percentile and high PTH concentration were the parameters associated with 25(OH)D level < 75 nmol/L. CONCLUSION: The prevalence of hypovitaminosis D in healthy Thai children is very high, despite their exposure to sunlight, and that prevalence increases in children with a high BMI percentile. As a result, a formal recommendation for vitamin D supplementation in Thai children should be considered.

Comparative Fasting Bioavailability of 2 Cilostazol Formulations in Healthy Thai Volunteers: An Open-Label, Single-Dose, Randomized, 2-Way Crossover Study.

OBJECTIVE: To evaluate the bioequivalence of50 mg cilostazol tablets manufactured locally (Citazol®) and originally (Pletaal®) in healthy Thai volunteers. MATERIAL AND METHOD: An open-label, single dose, randomized, two-period, two-sequence, crossover study in 30 healthy volunteers. Each volunteer received a 50 mg cilostazol tablet of bothformulations with a washoutperiodofat least 14 days. Blood samples were obtained atpre-dose and over 48 hours after dosing. Cilostazolplasma concentrations were quantified by using liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: The 30 volunteers completed the entire study. The geometric mean ratios (GAM) (test/reference) between the two formulations of cilostazol were 112.38% (101.70%-124.19%) for Cmax; 103.66% (96.06%-111.86%) for AUC0-48; and 95.14% (86.12%-105.12%)forAUC0-∞. There was no statistical difference ofthe Tmax between the twoformulations (p>0.05). No serious adverse events related to the studied drugs were found. CONCLUSION: No significant difference in the analyzed pharmacokineticparameters was found between the twoformulations of 50 mg cilostazol tablets. Therefore, it can be concluded that these two cilostazol tablet formulations were considered bioequivalent.

Role of meditation in reducing sympathetic hyperactivity and improving quality of life in lupus nephritis patients with chronic kidney disease.

BACKGROUND: Lupus nephritis is an important leading cause of chronic kidney disease (CKD) among the young population in Thailand. Systemic lupus erythematosus (SLE) is often characterized by the presence of sympathetic hyperactivity, which results in a perishing outcome. Some physiological studies reveal that meditation may reduce this autonomic dysfunction. The authors hypothesized that meditation could be beneficial in alleviating the sympathetic hyperactivity and improving quality of life in lupus nephritis patients with CKD. MATERIAL AND METHOD: The authors performed a prospective pilot study, which enrolled lupus nephritis patients and categorized enrollees into meditation group and control group. Method of meditation was instructed by an expert in Buddhist studies for a duration of 60 minutes every month. Participants in the intervention group were advised to meditate every day for 24 weeks. To evaluate change in sympathetic activity, normetanephrine level was measured at beginning and the end of study and compared between both groups. Quality of life was determined by SF-36. Heart rate variability was also assessed in meditation group. RESULTS: Thirty eligible patients were recruited into the study. Fifteen patients were stratified in the meditation group and 15 patients in the control group. After meditation for 6 months, serum normetanephrine level decreased, but without statistical significance (0.105 vs. 0.059, p = 0.28). The reduction in normetanephrine level was also observed in the control group (p = 0.11). In the aspect of quality of life, scores of physical and mental components improved significantly. In meditation group, physical component score increased from 21.4 (5.0-50.2) to 62.2 (51.8-88.4) points (p < 0.01) and mental score increased from 16.9 (4.4-46.0) to 72.4 (45.1-81.6) points (p < 0.01). Quality of life score in the meditation group significantly increased more than in control group (p < 0.01). The parameter of heart rate variability in time and frequency domain also improved in the meditation group. CONCLUSION: In lupus nephritis patients with CKD, meditation shows a trend of benefits in reducing sympathetic overactivity and improving quality of life. Our results support the important role of meditation as a valuable adjunctive treatment of lupus nephritis with CKD.

Plasma concentrations of bupivacaine after spinal anesthesia with single shot femoral nerve block and periarticular injection in total knee arthroplasty.

OBJECTIVE: To determine the plasma concentrations of bupivacaine and toxicity after periarticular injection (PAI) combined with spinal anesthesia and femoral nerve block (FNB). MATERIAL AND METHOD: Forty-three patients scheduled for unilateral total knee arthroplasty (TKA) were enrolled in the prospective observational study. The dose of bupivacaine for spinal anesthesia was adjusted by the attending anesthesiologist. The single-shot femoral nerve block (FNB) and periarticular injection (PAI) were performed with 20 ml of 0.5% bupivacaine and 20 ml of 0.25% bupivacaine respectively. Venous blood samples from antecubital vein were collected at 60 minutes after femoral nerve block and at the time before periarticular injection, then at 15, 30, 45, and 60 minutes afterwards. Plasma bupivacaine concentrations were analyzed, using a high performance liquid chromatography with tandem mass spectrometry. RESULTS: Ten males and 32 females, ASA I-II were included. The highest median plasma concentration was 586.22 ng/ml (min = 245.39, max = 1,614.36) at 45 minutes after periarticular injection. The maximum plasma bupivacaine concentration was 1,709.71 ng/ml at 60 minutes after periarticular injection. No clinical toxicity was encountered CONCLUSION: The plasma concentration of bupivacaine in patients performed periarticular injection with 20 ml of 0.25% bupivacaine after spinal anesthesia and single-shot femoral nerve block with 20 ml of 0.5% bupivacaine is below the plasma toxic level.

Prevalence of hyperkalemia in adult patients taking spironolactone and angiotensin converting enzyme inhibitors or angiotensin receptor blockers.

BACKGROUND: Hyperkalemia is common when spironolactone and angiotensin converting enzyme inhibitors (ACEls) or angiotensin receptor blockers (ARBs) are combined. OBJECTIVE: To determine the prevalence and risk factors of hyperkalemia in adult patients taking spironolactone and ACEls or ARBs. MATERIAL AND METHOD: A retrospective descriptive study was conducted. Adult patients taking spironolactone and ACEls or ARBs who visited the outpatient department of Siriraj Hospital between January and December 2009 were included. Exclusion criteria were chronic kidney disease patients who had undergone dialysis and patients with hyperkalemia from other causes. The authors defined hyperkalemia as serum potassium of more than 5.0 mmol/L. RESULTS: Five hundred thirty four patients were included during the study period. The prevalence of hyperkalemia was 11.2% (60 patients). The risk factors of hyperkalemia were chronic kidney disease (OR 2.47, 95% CI 1.07-5. 70), initial serum potassium level > 4.0 mmol/L (OR 2.65, 95% CI 1.44-4.88), and dosing of spironolactone more than 25 mg per day (OR 2.42, 95% CI 1.23-4.74). CONCLUSION: The prevalence of hyperkalemia in adult patients taking spironolactone and ACEIs or ARBs is 11.2%. Risk of hyperkalemia is chronic kidney disease, high serum potassium, and high spironolactone use.

Plasma concentrations of bupivacaine after spinal anesthesia with single shot femoral nerve block in total knee arthroplasty.

BACKGROUND: Femoral nerve block is commonly established for postoperative analgesia in total knee arthroplasty but no evidence of plasma bupivacaine level has been reported. OBJECTIVE: Determine the plasma concentrations of bupivacaine in patients who had single-injection of femoral nerve block. MATERIAL AND METHOD: A prospective observational study was undertaken with 25 patients scheduled for unilateral total knee arthroplasty under spinal anesthesia and single shot femoral nerve block with 20 mL of 0.5% bupivacaine. Venous blood samples were collected at 0, 5, 10, 15, 30, 60, 90, and 120 minutes after femoral nerve block. Plasma bupivacaine levels were analyzed by high performance liquid chromatography with tandem mass spectrometry. RESULTS: Four males and 21 females, ASA I-II were enrolled in the present study. Mean age, body mass index, and serum albumin level were 69.9 +/- 5.95 years, 27 +/- 3.67 kg/m2, and 4.46 +/- 0.26 mg/dL, respectively. The median of peak plasma concentration was 538.35 ng/mL (min = 176.30, max = 1,383.99) at 60 minutes after femoral nerve block, while the maximal plasma concentration of bupivacaine was 1,883.39 ng/mL at 10 minutes. None showed signs or symptoms of bupivacaine toxicity. CONCLUSION: Peak plasma concentrations of bupivacaine were demonstrated at 60 minutes after a single shot femoral nerve block, and no signs or symptoms of bupivacaine toxicity were observed Therefore, single shot femoral nerve block with 20 mL of 0.5% bupivacaine is safe.

Phase II clinical trial of Ayurved Siriraj Wattana Recipe for symptomatic relief in patients with osteoarthritis of the knee.

BACKGROUND: Osteoarthritis of the knee is one of the most common public health problems in Thailand and throughout the world. It causes disability, with pain and loss of function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common treatment modality to relieve pain for OA, but can cause undesirable adverse effects. Effective and safer alternative treatments for OA are urgently needed. Among the many kinds, Ayurved Siriraj Wattana Recipe has been widely used in humans for a long time. The components of the recipe probably were related with many systems of the body such as the immune system and the gastrointestinal system and it may have anti-inflammatory activity as well as anti-oxidative capacity. OBJECTIVE: Determine the efficacy of Ayurved Siriraj Wattana Recipe for knee osteoarthritis in a randomized, open-label, diclofenac-controlled trial for 12 weeks. The trial has been approved from Siriraj Institutional Review Board (SIRB), Faculty of Medicine, Siriraj Hospital, Mahidol University. MATERIAL AND METHOD: Analyze the 12-item Oxford, defined as 5-point Likert scales of pain and functional activity. The secondary assessment included 10-cm VAS pain assessment tool as well as, patients' and physician's global efficacy assessment. RESULTS: "12-Item Oxford" revealed that patients had mild problems in terms of function and pain with an average function score observed between groups (p = 0.6). The average pain score at 12 weeks' follow-up was not significantly different in the Wattana group compared with the diclofenac group (p = 0.3). Responses with no differences included the mean 10-cm VAS that assessed pain at 12 weeks' follow-up in both groups. There were no significant differences in the patients' and physician's global efficacy assessment with patients in both groups. There were no differences in the frequent of adverse events between groups. In addition, there were no significant differences in the patients' and physician's global safety assessment between groups. CONCLUSION: The present, diclofenac-controlled trial concludes that Ayurved Siriraj Wattana Recipe treatment could be an effective treatment of pain in knee OA at 12 weeks.

Safety and immunogenicity of intradermal administration of fractional dose CoronaVac®, ChAdOx1 nCoV-19 and BNT162b2 as primary series vaccination.

There is a limited supply of COVID-19 vaccines, with less than 20% of eligible populations in low-income countries having received one dose. Intradermal delivery of fractional dose vaccines is one way to improve global vaccine access, but no studies have reported data on intradermal delivery of COVID-19 primary series vaccination. We conducted a pilot study to examine the safety and immunogenicity of three intradermal primary series regimens - heterologous regimen of CoronaVac and ChAdOx1 (CoronaVac-ChAdOx1), homologous regimen of ChAdOx1 (ChAdOx1-ChAdOx1), and homologous regimen of BNT162b2 (BNT162b2-BNT162b2). Each dose was 1/5th or 1/6th of the standard dose. Two additional exploratory arms of intradermal vaccination for the second dose following an intramuscular first dose of ChAdOx1 and BNT162b2 were included. Intradermal vaccination was found to be immunogenic and safe. The antibody responses generated by the intradermal primary series were highest in the BNT162b2 arms. The anti-receptor binding domain (anti-RBD) IgG concentration following fractional dose intradermal vaccination was similar to that of standard dose intramuscular vaccination of the same regimen for all study arms except for BNT162b2. The BNT162b2 intradermal series generated a lower antibody concentration than the reference intramuscular series, despite generating the highest antibody concentration of all three intradermal primary series regimens. Neutralizing antibody responses against the SARS-CoV-2 ancestral strain were consistent with what was observed for anti-RBD IgG, with lower titers for SARS-CoV-2 variants. Neutralizing titers were lowest against the omicron variant, being undetectable in about a quarter of study participants. T-cell responses against spike- and nucleocapsid-membrane-open reading frame proteins were also detected following intradermal vaccination. Adverse effects following intradermal vaccination were generally comparable with post-intramuscular vaccination effects. Taken together, our data suggest that intradermal vaccination using 1/5th or 1/6th of standard COVID-19 intramuscular vaccination dosing were immunogenic with tendency of lower systemic adverse reactions than intramuscular vaccination. Our findings have implications in settings where COVID-19 vaccines are in shortage.

Evaluation of the Safety and Immunogenicity of Fractional Intradermal COVID-19 Vaccines as a Booster: A Pilot Study.

Intradermal vaccination using fractional dosages of the standard vaccine dose is one strategy to improve access to COVID-19 immunization. We conducted a pilot study in healthy adults in Thailand to evaluate the safety and immunogenicity of intradermal administration of fractional doses of ChAdOx1 (1/5th of standard dosage) or BNT162b2 (1/6th of standard dosage) to individuals previously vaccinated (prime) with two-dose intramuscular CoronaVac, ChAdOx1 or BNT162b2. Following an initial immunogenicity exploratory phase for each vaccine combination group (n = 10), a total of 135 participants (n = 45 per group) were recruited to 3 groups (CoronaVac prime-intradermal BNT162b2 boost, CoronaVac prime-intradermal ChAdOx1 boost and ChAdOx1 prime-intradermal BNT162b2 boost) and their immunogenicity data were compared to a previous cohort who received the same vaccine intramuscularly. Two weeks following booster vaccination, neutralizing antibodies against the delta variant were similar between the participants who received intradermal and intramuscular vaccination. However, neutralizing antibodies against the omicron variant in the intradermal BNT162b2 boost groups were ~6-fold lower, while the levels in the ChAdOx1 boost group were similar compared to their respective vaccine regimen given intramuscularly. The intradermal booster significantly increased spike-specific T cell responses in all three groups from pre-booster levels. Local and systemic adverse reactions were milder in intradermal compared to intramuscular injections. Further studies are needed to evaluate the clinical relevance of these findings and the feasibility of administration of intradermal COVID-19 vaccines.

Bioequivalence study of 10 mg ramipril tablets in healthy Thai volunteers.

OBJECTIVE: To determine the bioequivalence of 10 mg dose of ramipril tablets between the test product (Ramtace 10 mg, Unison Laboratories, Thailand) and the reference product (Tritace 10 mg, Aventis Pharma SPA, Italy). MATERIAL AND METHOD: The present study was carried out with a single dose, 2-treatment, 2-period, 2-sequence randomized crossover design under fasting condition with a minimum of 14 days washout period in 24 healthy Thai male and female volunteers. Plasma samples for determination of ramipril and ramiprilat were obtained pre-dose and at frequent intervals for up to 72 h post dose. Ramipril and ramiprilat plasma concentrations were quantified by a validated method employing high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). All ofthe pharmacokinetic parameters were investigated using non-compartmental analysis. RESULTS: The result demonstrated the 90% confidence interval (90%CI) of the geometric mean ratio (test/reference) of C max, AUC(0-72) and AUC(0-infinity) of ramipril were 97.26% (84.50%-111.93%), 100.70% (89.47%-113.34%) and 100.29% (88.90% 113.15%), respectively. For ramiprilat, the 90% CI for C max, AUC(0-72), and AUC(0-infinity) were 108.87% (103.00%-115.07%), 104.93% (100.50%-109.55%) and 103.30% (98.03%-108.85%), respectively. CONCLUSION: the 90% confidence intervals for log-transformed geometric mean test/reference formulation ratios of primary parameters were entirely within 80.00%-125.00%. Thus, it can be concluded that the test formulation was bioequivalent to the reference formulation.

Effect of Ayurved Siriraj herbal recipe Chantaleela on platelet aggregation.

INTRODUCTION: Ayurved Siriraj Chantaleela recipe is a traditional Thai remedy consisting of eight medicinal plants, which is employed for the treatment of fever. OBJECTIVE: To investigate the effects of Ayurved Siriraj Herbal recipe Chantaleela on platelet aggregation. STUDY DESIGN: Clinical research; ex vivo with before and after study design. MATERIAL AND METHOD: Twelve healthy male and female volunteers participated in the present study. Platelet aggregation test before Chantaleela ingestion was done as a control. After administration of 750 mg Chantaleela (3 x 250 mg tablets) every 8 hours for 3 doses, platelet aggregation was measured 8 hours following the first dose using an aggregometer and microplate reader. Adrenaline (Adr) and adenosine diphosphate (ADP) were used as platelet stimulants. Platelet aggregation was measured again at 32 hours and 8-10 days after the first dose. RESULTS: All of the participants completed the present study without any adverse event. Ayurved Siriraj Chantaleela did not affect platelet aggregation; neither Adr nor ADP were used as platelet agonists in both aggregometer and microplate reader Subgroup analysis revealed no significant change in platelet aggregation after Chantaleela administration according to the control for both male and female groups. The same results were also obtained in other subgroup analysis including hyperaggregation group, hypo-normal aggregation group. CONCLUSION: From the present study, normal dose of Chantaleela for alleviation of fever does not have an effect on either platelet aggregation or platelet numbers. It may conclude that the present study supports the safety use of Chantaleela for relieving fever as platelet status does not need to be taken into consideration.

Bioequivalence study of 50 mg sertraline tablets in healthy Thai volunteers.

OBJECTIVE: To determine the bioavailability of 50 mg sertraline tablets between the test product (Zotaline, M&H Manufacturing Co., Ltd, Thailand) and the reference product (Zoloft, Pfizer Australia Pty Ltd, Australia). MATERIAL AND METHOD: An open-labeled, single dose, 2-treatment, 2-period, 2-sequence, randomized crossover study under fasting conditions with 14 days washout period was conducted in 24 healthy Thai volunteers. Blood samples were collected before dosing and at frequent intervals for up to 96 h post dose. Analysis of sertraline concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. RESULTS: Twenty-four volunteers completed both treatment periods. Pharmacokinetic parameters were determined using the non-compartment model. The 90 percent confidence intervals of the geometric mean ratios (test/reference) of C(max) 104.47% (96.64%-112.93%), AUC(0-96) 108.06% (100.71%-115.94%) and AUC(0-infinity) 108.39% (100.93%-116.40%) fell within the equivalence range (80%-125%). There was no significant difference of the T(max) parameter between the two formulations (p > 0.05). No serious adverse events related to the study drugs were found. CONCLUSION: The two formulations of sertraline tablets were bio-equivalent in Thai healthy volunteers.

Bioequivalence study of 500 mg glucosamine sulfate in Thai healthy volunteers.

BACKGROUND AND OBJECTIVE: Glucosamine sulfate is widely used to relieve symptoms from osteoarthritis. The present study was conducted in order to determine pharmacokinetic and assess the in-vivo bioequivalence of two different hard capsule formulations of glucosamine sulfate when administered as equal dose of 500 mg. The two formulations contained different salt form where reference product is NaCl and test product is KCl. MATERIAL AND METHOD: A randomized, single dose, two-treatment, two-period, two-sequence crossover study was conducted. Twenty-four healthy volunteers were recruited at Siriraj Clinical Research Unit. Each subject received a dose of 500 mg glucosamine sulfate of both formulations with at least one-week washout period. Blood samples were collected over 24 h after the oral administration. The plasma fractions were analyzed for glucosamine using a liquid chromatography-mass spectrometry (LC-MS/MS). RESULTS: Twenty-four volunteers were enrolled in the present study Pharmacokinetic parameters were determined using the non-compartment model. The 90% confidence intervals of the mean ratios (test/reference) of C(max) (93.69%; ranged from 86.68%-113.32%) and AUC(0-t), (97.73; ranged from 87.38%-112.62%) fell within the acceptable range (80-125%) for bioequivalent eligibility. Both preparations were well tolerated and had a few non-serious adverse events. CONCLUSION: The glucosamine sulfate containing KCl (test product) is bioequivalent to glucosamine sulfate containing NaCl (reference product) in terms of rate and extent of absorption.

Evaluation of the safety and relative bioavailability of a new dihydroartemisinin tablet formulation in healthy Thai volunteers.

A new dihydroartemisinin (DHA) tablet formulation has been developed by the Thai Government Pharmaceutical Organization (GPO). In this report, its in vitro dissolution and in vivo pharmacokinetics as well as its safety in healthy volunteers were evaluated, using the DHA tablet made by Dafra Pharma NV as a reference. A two-period crossover clinical study design was utilised. Twenty-four volunteers were randomly allocated to two sequences (12 volunteers in each) to receive a 200mg single oral dose of either the GPO or Dafra formulation with a wash-out period of 5-7 days. In vitro, the GPO formulation dissolved more readily. In vivo, the GPO formulation had a higher maximum plasma concentration and approximately 149% (90% CI 125-179%) greater bioavailability. Both formulations were well tolerated. Interestingly, significant decreases in haemoglobin and haematocrit values (P<0.001) were noted following administration of one dose of DHA (decrease of 0.73 g/dl haemoglobin and 2.0% haematocrit compared with baseline) or two doses of DHA (decrease of 0.95 g/dl haemoglobin and 3.3% haematocrit compared with baseline). The second dose was associated with additional toxicity compared with one dose with regard to haematocrit (P<0.001) but not haemoglobin. This finding warrants further investigation, since the drug will be used for the treatment of malaria in which anaemia is a consequence.

Bioequivalence study of 30 mg pioglitazone tablets in Thai healthy volunteers.

OBJECTIVE: To compare the bioequivalent parameters of 30 mg pioglitazone tablets manufactured locally (Glista) and originally (Actos). MATERIAL AND METHOD: A randomized, single dose, two-treatment, two-period, two-sequence crossover study was conducted Twenty-four healthy volunteers were recruited at Siriraj Clinical Research Unit. Each subject received a 30 mg pioglitazone tablet of both formulations with at least a week washout period Blood samples were collected over 48 h after the oral administration. The plasma fractions were analyzed for pioglitazone using a liquid chomatography-mass spectrometry (LC-MS/MS). RESULTS: Twenty-four volunteers enrolled in the present study. Pharmacokinetic parameters were determined using the non-compartment model. The 90 percent confidence intervals of the mean ratios (test/reference) of Cmax (86.2687-113.7313%), A UC0-->t(85. 7139-114.2861%) and AUC0-->infinity (81.7820-118.2180%) fell within the acceptable range (80-125%) for bioequivalent eligibility. Both preparations were well tolerated and had afew non-serious adverse events. CONCLUSION: The 2-tablet preparations of pioglitazone were bioequivalent in Thai healthy volunteers.

A Case-Control Study of Involvement of Oxidative DNA Damage and Alteration of Antioxidant Defense System in Patients with Basal Cell Carcinoma: Modulation by Tumor Removal.

Oxidative damage has been suggested to play a role in the pathogenesis of basal cell carcinoma (BCC). This study illustrated an involvement of oxidative DNA damage and changes in antioxidant defenses in BCC by conducting a case-control study (24 controls and 24 BCC patients) and assessing urinary 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dGuo), plasma antioxidant defenses including catalase (CAT), glutathione peroxidase (GPx), NQO1, and total superoxide dismutase (SOD) activities, and glutathione (GSH) levels before surgery and 1 month after surgery. 8-oxo-dGuo expressions as well as protein and mRNA expressions of DNA repair enzyme hOGG1 and antioxidant defenses (CAT, GCLC, GPx, Nrf2, and MnSOD) in nonneoplastic epidermis of control and BCC tissues were also determined. This study observed induction in urinary 8-oxo-dGuo, increased 8-oxo-dGuo expression, and reduced hOGG1 protein and mRNA in BCC tissues, decreased activities of CAT, GPx, and NQO1, but elevated SOD activities and GSH levels in BCC patients and reduction of all antioxidant proteins and genes studied in BCC tissues. Furthermore, decreased plasma antioxidant activities in BCC patients were restored at 1 month after operation compared with preoperative levels. Herein, we concluded that BCC patients were associated with oxidative DNA damage and depletion of antioxidant defenses and surgical removal of BCC correlated with improved redox status.

Maternal Vitamin D Status and Its Related Factors in Pregnant Women in Bangkok, Thailand.

BACKGROUND: There are few data focusing on the prevalence of vitamin D deficiency in tropical countries. OBJECTIVES: We determined the vitamin D status in pregnant women and examined the factors associated with vitamin D deficiency. DESIGN AND METHODS: A cross-sectional study of 147 pregnant Thai women aged 18-45 years at Siriraj Hospital (a university hospital in Bangkok, Thailand) was undertaken. Clinical data and plasma levels of 25-hydroxyvitamin D [25(OH)D], intact parathyroid hormone (iPTH), calcium, albumin, phosphate and magnesium were obtained in pregnant women at delivery. RESULTS: The prevalence of hypovitaminosis D [defined as 25(OH)D <75 nmol/L] in pregnant women at delivery was 75.5% (95% confidence interval (CI), 67.7-82.2%). Of these, vitamin D insufficiency [defined as 25(OH)D 50-74.9 nmol/L] was found in 41.5% (95% CI, 33.4-49.9%) and vitamin D deficiency [25(OH)D <50 nmol/L] was found in 34.0% (95% CI, 26.4-42.3%) of women. The mean 25(OH)D concentration was 61.6 ± 19.3 nmol/L. The correlation between 25(OH)D and iPTH was weak (r = -0.29, P<0.01). Factors associated with vitamin D deficiency by multiple logistic regression were: pre-pregnancy body mass index (BMI in kg/m2, odds ratio (OR), 0.88, 95% CI 0.80-0.97, P = 0.01) and season of blood collection (winter vs. rainy, OR, 2.62, 95% CI 1.18-5.85, P = 0.02). CONCLUSIONS: Vitamin D deficiency is common among pregnant Thai women. The prevalence of vitamin D deficiency increased in women who had a lower pre-pregnancy BMI and whose blood was collected in the winter. Vitamin D supplementation may need to be implemented as routine antenatal care.

Prevalence and risk factors for chloroquine maculopathy and role of plasma chloroquine and desethylchloroquine concentrations in predicting chloroquine maculopathy.

AIM: To determine the prevalence and to identify the risk factors of chloroquine maculopathy (CM), and to evaluate the association of plasma chloroquine (CQ) and desethylchloroquine (DCQ) levels and CM. METHODS: Rheumatoid arthritis (RA) patients who had taken CQ for at least 6 months and stable CQ dosage for at least 2 months were included. CM was diagnosed by dilated ocular examination and automated visual field. Plasma CQ and DCQ levels were determined by liquid chromatography tandem mass spectrometry method. Logistic regression was used to explore risk factors associated with CM. RESULTS: One hundred and ninety-three patients were included with median CQ duration (range) of 50.2 months (6.0-269.8) and cumulative dose of 137.4 g (16.4-1226.5). The prevalence of CM was 13.5%. Factors associated with CM identified from univariate analysis were age > 60 years, and creatinine clearance with odds ratio (OR) (95%CI) of 5.79 (2.42, 13.84), and 0.98 (0.96, 1.00). In multivariate analysis, older age, usage > 5 years, and current dose from 2.5 mg/kg ideal body weight [IBW]/day were the factors significantly associated with CM with OR of 5.89 (2.38, 14.57), 2.94 (1.10, 7.83), and 3.32 (1.04, 10.60), respectively, while plasma CQ and DCQ showed no association with CM. CONCLUSIONS: The prevalence of CM was 13.5% among RA patients taking CQ for at least 6 months. Age > 60 years, duration of CQ usage > 5 years and current CQ dose ≥2.5 mg/kg IBW/day were the risk factors for CM. The plasma CQ or DCQ levels demonstrated no correlation in developing CM.