Bioequivalence evaluation of 320 mg gemifloxacin tablets in healthy volunteers.

This study was done to compare the bioavailability of a new tablet formulation of gemifloxacin (gemifloxacin 320 mg/tablet) with that of the reference product (factive 320 mg/tablet). The bioequivalence of a single dose (320 mg) was assessed for gemifloxacin included in the test and reference products by comparing the pharmacokinetic parameters derived from the plasma concentration-time profiles following administration to 24 healthy male volunteers in a balanced, 2-period, 2-sequence, 2-way crossover design. Plasma concentrations of gemifloxacin were analyzed by a validated and sensitive HPLC assay developed in-house. The mean plasma concentration-time profiles are almost superimposable. 18 ANOVAs were performed to compare gemifloxacin plasma levels of the two formulations at each sampling time and there were no statistical differences between the two formulations. The parameters used to measure bioavailability were AUC0-t, AUC0-infinity and Cmax and they were calculated by a model-independent method. The parametric 90% confidence intervals of the mean values for the test/reference ratio were in each case well within the bioequivalence acceptable boundaries of 80-125% for AUCo-t, AUC0-infinity and Cmax. Data obtained in this study prove, by appropriate statistical methods, the essential similarity of plasma levels of gemifloxacin from the test product with those from the reference product suggesting equal clinical efficacy of these two products.

Comparative bioavailability study of cefixime (equivalent to 100 mg/5 ml) suspension (Winex vs Suprax) in healthy male volunteers.

This investigation was carried out to evaluate the bioavailability of a new suspension formulation of cefixime (100 mg/5 ml), Winex, relative to the reference product, Suprax (100 mg/5 ml) suspension. The bio-availability study was carried out in 24 healthy male volunteers who received a single oral dose (200 mg) of the test (A) and the reference (B) products on 2 treatment days after an overnight fast of at least 10 hours. The treatment periods were separated by a one-week washout period. A randomized, balanced two-way crossover design was used. After dosing, serial blood samples were collected over a period of 16 hours. Plasma concentrations of cefixime were analyzed using a sensitive high-performance liquid chromatographic assay. The pharmacokinetic parameters for cefixime were determined using standard non-compartmental method. The parameters AUC(0-t), AUC(0-infinity), Cmax, Kel, t1/2 and Cmax/AUC(0-infinity) were analyzed statistically using raw and log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pnfinity harmacokinetic parameters: AUC(0-t), AUC(0-infinity) Cmax, and Cmax/AUC(0-infinity) were within the range 80 - 125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax, and Cmax/AUC(0-infinity) were 88.93 - 107.10%, 89.09 - 107.11%, 89.63 - 108.58% and 96.85 - 105.29%, respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), and Cmax using the Schuirmann's two one-sided t-tests. Therefore, the two formulations were considered to be bioequivalent.

Comparative bioavailability study of doxycycline hyclate (equivalent to 100 mg doxycycline) capsules (doxycin vs vibramycin) for bioequivalence evaluation in healthy adult volunteers.

This investigation was carried out to evaluate the bioavailability of a new capsule formulation of doxycycline (100 mg), doxycin, relative to the reference product, vibramycin (100 mg) capsules. The bioavailability was carried out in 24 healthy male volunteers who received a single dose (100 mg) of the test (A) and the reference (B) products after an overnight fast of at least 10 hours on 2 treatment days. The treatment periods were separated by a 2-week washout period. A randomized, balanced 2-way cross-over design was used. After dosing, serial blood samples were collected for a period of 48 hours. Plasma concentrations of doxycycline were analyzed by a sensitive and validated high-performance liquid chromatography assay. The pharmacokinetic parameters for doxycycline were determined using standard noncompartmental methods. The parameters AUC(0-t), AUC(0-infinity), Cmax, K(el), t(1/2) and Cmax/AUC(0-infinity) were analyzed statistically using log-transformed data. The time to maximum concentration (tmax) was analyzed using raw data. The parametric 90% confidence intervals of the mean values of the pharmacokinetic parameters: AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were within the range 80-125% which is acceptable for bioequivalence (using log-transformed data). The calculated 90% confidence intervals based on the ANOVA analysis of the mean test/reference ratios of AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) were 95.98-109.56%, 92.21 to 107.66%, 93.90-112.56%, and 96.0 to 106.91% respectively. The test formulation was found bioequivalent to the reference formulation with regard to AUC(0-t), AUC(0-infinity), Cmax and Cmax/AUC(0-infinity) by the Schuirmann's two 1-sided t-tests. Therefore, the 2 formulations were considered to be bioequivalent.

High-performance liquid chromatographic determination of furosemide in plasma and urine and its use in bioavailability studies.

A sensitive, selective and efficient reversed-phase high-performance liquid chromatographic (HPLC) method is reported for the determination of furosemide in human plasma and urine. The method has a sensitivity limit of 5 ng/ml in plasma, with acceptable within- and between-day reproducibilities and good linearity (r2>0.99) over a concentration range from 0.05 to 2.00 microg/ml. The one-step extract of furosemide and the internal standard (warfarin) from acidified plasma or urine was eluted through a muBondapak C18 column with a mobile phase composed of 0.01 M potassium dihydrogenphosphate and acetonitrile (62:38, v/v) adjusted to pH 3.0. Within-day coefficients of variation (C.V.s) ranged from 1.08 to 8.63% for plasma and from 2.52 to 3.10% for urine, whereas between-day C.V.s ranged from 4.25 to 10.77% for plasma and from 5.15 to 6.81% for urine at three different concentrations. The minimum quantifiable concentration of furosemide was determined to be 5 ng/ml. The HPLC method described has the capability of rapid and reproducible measurement of low levels of furosemide in small amounts of plasma and urine. This method was utilized in bioavailability/pharmacokinetic studies for the routine monitoring of furosemide levels in adults, children and neonate patients.

Comparative bioavailability of two tablet formulations of ranitidine hydrochloride in healthy volunteers.

This investigation was carried out to evaluate the bioavailability of a new tablet formulation of ranitidine HCl (300 mg), Ranid, relative to the reference product, Zantac, (300 mg) tablets. The bioavailability was carried out on 24 healthy male volunteers who received a single dose (300 mg) of the test (T) and the reference (R) products in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 16 hours. Plasma harvested from blood was analyzed for ranitidine by a sensitive and validated high-performance liquid chromatographic assay. The maximum plasma concentration (Cmax), area under the plasma concentration time curve up to the last measurable concentration (AUC0-t), and to infinity (AUC0-infinity) and the absorption rate (Cmax/AUC0-infinity) were analyzed statistically under the assumption of a multiplicative model. The time to maximum concentration (Tmax) was analyzed assuming an additive model. The parametric confidence intervals (90%) of the mean values of the pharmacokinetic characteristics (AUC0-t, AUC0-infinity), Cmax and Cmax/AUC0-infinity) for T/R ratio were in each case well within the bioequivalence acceptable range of 80-125%. The test formulation was found bioequivalent to the reference formulation by the Schuirmann's two one-sided t-tests and by Wilcoxon Mann Whitney two one-sided tests procedure. Therefore, the 2 formulations were considered to be bioequivalent.

Comparative bioavailability of two tablet formulations of acyclovir in healthy volunteers.

This investigation was carried out to evaluate the bioavailability of a new tablet formulation of acyclovir (400 mg), Clovir, relative to reference product, Zovirax (400 mg) tablets. The 2 brands were found to be similar in weight variation, disintegration time, dissolution, and assay as stipulated by the USPXXIII, as well as by the manufacturer. The bioavailability was carried out on 24 healthy male volunteers who received a single dose (400 mg) of the test (T) and the reference (R) products in the fasting state, in a randomized balanced 2-way crossover design. After dosing, serial blood samples were collected for a period of 16 hours. Plasma harvested from blood was analyzed for acyclovir by a sensitive and validated high-performance liquid chromatographic assay. The maximum plasma concentration (Cmax), area under the plasma concentration-time curve up to the last measurable concentration (AUC0-t), and to infinity (AUC0-infinity), and the absorption rate (Cmax/AUC0-infinity) were analyzed statistically under the assumption of a multiplicative model. The time to maximum concentration (Tmax) was analyzed assuming an additive model. The parametric confidence intervals (90%) of the mean values of the pharmacokinetic characteristics (AUC0-t, AUC0-infinity, Cmax, Cmax/AUC0-infinity) for T/R ratio were in each case, well within the bioequivalence acceptable range of 80-125%. The test formulation was found bioequivalent to the reference formulation by the Schuirmann's two 1-sided t tests and by Wilcoxon Mann Whitney two 1-sided tests procedure. Therefore, the 2 formulations were considered to be bioequivalent.

Care of asthmatic patients in primary health care centers.

This is a retrospective study of the medical records of asthamtics using a predesigned form. The purpose of the study is to define the number of patients registered as asthamatics at a random selection of primary health care centers (PHCCs) in Riyadh and to describe sociodemographic, clinical and management characteristics of this population of asthmatics with a view to recommending changes which might improve the care for asthma patients. Patients from 60 primary health care centers were studied. There were 2081 asthamatic patients found in the studied PHCCs (out of 255,145 surveyed), giving a rate of 0.8%. Out of all the patients, 32.8% were children 16 years of age or below and 24.7% were above 5 years of age. The male to female ratio was 1.2:1. The presenting symptoms were cough in 82.3% and shortness of breath 64.8%. Atopic disorders such as eczema and allergic rhinitis were recorded in 27.7%. PHCCs diagnosed 61.9% depending on history and clinical examination. Out of all patients, 10.6% did not utilize a PHCC, 29.5% were referred to a specialist and 8.7% needed admission to the hospital one or more times. Oral salbutamol was used in more than 45.7% of the patients. The number of registered bronchial asthma patients at the PHCCs was very low. Even when registered, asthmatic patients are getting suboptimal care. The present study provides a basis for intervention and a baseline from which to measure the benefits of intervention. It also provides the strongest possible support for the Ministry of Health, who recently initiated a National Asthma Program.

Compliance with short-term antibiotic therapy among patients attending primary health centres in Riyadh, Saudi Arabia.

Non-compliance results in several undesired consequences. Admissions due to non-compliance have been estimated to account for up to 10.5% of all admissions to hospital. There seems to be very little data about compliance in Saudi Arabia. The present study addressed the problem of non-compliance with short-term antibiotic therapy in patients attending Primary Health Centres (PHC). The data were collected from five different centres selected randomly from the 53 centres in the Riyadh area, Saudi Arabia. A five-part questionnaire was designed and used to collect data. Different parts were required to be completed by patient, doctor, pharmacist and social worker. At the end of the study period 414 questionnaires were suitable for evaluation. Paediatric patients (< 15 years old) constituted 65.9% of the sample. Compliance was noted in 67.8%. Those who missed three doses or less and more than three doses were 22.7% and 9.4% respectively. Factors which appeared to enhance patient compliance were: parental involvement (p < 0.001), unemployment (p < 0.01), absence of psychiatric illness (p < 0.02) and early improvement of symptoms (p < 0.05). Reasons most frequently mentioned by patients for non-compliance were: rapid improvement of symptoms, bitter taste of drug(s), forgetfulness and frequent dosing. These reasons accounted for 73.7% of reasons for non-compliance. Our findings suggest that approximately two thirds of patients were compliant with their medications. It is also worth noting that approximately three quarters of patients were not compliant for reasons which could be minimised or removed by good patient counselling and effective communication with patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous Iron Saccharate in Hemodialysis Patients Receiving r-HuEPO.

A study was undertaken to evaluate the safety and efficacy of iron saccharate in regular haemodialysis (HD) patients receiving r-HuEPO. A total of 109 patients (57 males, 52 females, mean age 34.1 + 11.7 years) were included in the study, 64 of whom were iron deficient. The patients were divided into two groups. Group I (n = 58) received high dose iron saccharate (500 mg), intravenously (i.v.) (1-2 doses), and Group II (n = 51) received low dose iron saccharate (100 mg), i.v., thrice per week (5-10 doses). Results at four weeks showed a significant increment in hemoglobin (Hb), hematocrit (Hct), and serum ferritin in both groups. Two patients developed headache, fever and urticaria, and three patients developed fever in group I. None of the patients in group II developed any adverse reaction. Intravenous iron supplementation with iron saccharate in HD patients showing poor response to r-HuEPO, produced satisfactory Hct levels without major side effects and without the need to increase the dose of r-HuEPO. Commonly observed side effects were not seen with the low dose regimen.

Comparison of the effects of three haemodialysis membranes on vancomycin disposition.

Polysulfone (PSF) and polyacrylonitrile (PAN) were recently introduced haemodialysis (HD) membranes. The effect of each on vancomycin disposition was compared with cuprophan (SCE) in 12 chronic HD patients who received 14 infusions. Vancomycin (1 g) was infused over 1 hour, followed by three 4-hour HD sessions over 5 days, beginning 1 hour after the end of infusion. The intradialytic clearances of vancomycin were 73, 54 and 15 ml/min for PSF, PAN and SCE, respectively. At the end of the third HD session, vancomycin concentration dropped to subtherapeutic level (< 7.5 micrograms/ml) only in patients dialysed with PSF and PAN. The corresponding elimination half-lives (t1/2 beta) were 61, 60 and 86 hours for the three membranes, respectively. According to these findings, vancomycin should be given every three HD sessions for PSF and PAN. The dosage interval should be extended up to every 5 HD sessions for patients on SCE. The peak (mean +/- S.D.) obtained one hour after the end of infusion was 34.2 +/- 11.4 micrograms/ml, which is within the therapeutic range.

Intralesional treatment of cutaneous leishmaniasis with sodium stibogluconate antimony.

BACKGROUND: Cutaneous leishmaniasis represents a difficult disease to manage in endemic areas. Systemic treatment is hampered by both expense and compliance. Side effects may play a major role in this aspect as well. METHODS: The effectiveness of intralesional treatment of leishmaniasis was investigated. Seven hundred and ten patients were treated with injections of sodium stibogluconate intralesionally. The clinical diagnosis was confirmed by demonstrating the parasite in the smears obtained from the lesion. Fine insulin needle was used to infiltrate the lesion with sodium stibogluconate (0.5 to 1.0 mL). RESULTS: Generally eight injections were sufficient, but some of the complicated lesions needed up to 24 injections. Sixty-two percent of patients were men. The majority of the study population (64%) were children below 15 years of age. The results showed that 72% of lesions healed completely, 23.9% showed some improvement, while 4.1% showed some deterioration. Lesions of the lips, cheeks, chin, and neck healed faster than lesions in other parts of the body. Side effects were mild and limited to pain at the site of the injection and hyperpigmentation in those who were treated by folk medicine. CONCLUSIONS: Intralesional treatment is as effective as the standard systemic antimonials. It offers a less expensive alternative and a low side effects profile. Our findings confirmed the findings of earlier workers. It is recommended for treatment of cutaneous leishmaniasis in endemic areas.

Experimental treatment of Brucella melitensis infection in sheep with oxytetracycline alone or combined with streptomycin.

The efficacy of oxytetracycline (OTC) alone or combined with streptomycin in the treatment of 118 Najdi ewes believed to have been naturally infected with Brucella melitensis, was evaluated by culture of selected tissues and organs at slaughter. Groups of sheep were given 250, 500 or 1,000 mg of OTC intraperitoneally (i/p) daily for six weeks and in the respective groups at necropsy 52, 69 and 100% of sheep were found to be Brucella-free. Treatment with 250 mg OTC (daily for six weeks i/p) combined with 1,000 mg streptomycin (daily for three weeks intramuscularly) increased the percentage of Brucella-free sheep to 82%. When a group of sheep were each inoculated i/p with 1,000 mg of long-acting OTC every three days over a period of six weeks, 75% of them were Brucella-free at necropsy. B. melitensis was isolated from all (24) non-treated (control) sheep. The results showed that long-term treatment with a high dose of OTC alone had succeeded in eliminating B. melitensis from a group of 16 naturally infected sheep.