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PURPOSE: Colistin, which had not been used widely because of nephrotoxicity and neurotoxicity, has gained clinical importance in recent times due to the resurgence of multidrug-resistant Gram-negative bacilli. Very few studies, especially pharmacokinetic studies, have been performed with intravenous colistimethate sodium, and none in India. The aim of our study was to study the single-dose and steady-state pharmacokinetics of colistin in patients with multidrug-resistant Gram-negative bacilli infections. METHOD: This was a prospective open-label pharmacokinetic study done in an intensive care unit in a tertiary care hospital on 15 critically ill patients with proven multidrug-resistant Gram-negative bacilli infection. Colistimethate sodium was injected as intermittent intravenous infusions in accordance with the recommendations on the package insert. For patients weighing ≥ 60 kg with a normal renal function or with a creatinine clearance (CL(CR)) of between 20 and 50 ml/min, the drug was administered at 2 million international units (MIU) every 8 h; for those with a CL(CR) of 10-20 ml/min, the dose was 2 MIU every 12 h. Those patients who weighed <60 kg were administered 50,000 IU/kg/day in three divided doses at 8-h intervals. Both single-dose and steady-state pharmacokinetics of colistin were determined and correlated with clinical outcomes. RESULTS: A wide inter-individual variation was observed in pharmacokinetic parameters. The median (range) of the maximum plasma drug concentration/minimum inhibitory concentration (C(max)/MIC) ratio for Acinetobacter spp. was 13.4 (1.3-40.3) following the administration of a single dose of colistimethate sodium and 26.3 (0.9-64.9) at steady-state. For Pseudomonas spp., these values were 3.18 (1.6-23.1) following the single dose and 3.82 (2.3-10.9) at steady-state. For those patients whose cultures grew Acinetobacter spp., an optimum value of the C(max)/MIC ratio of >8 was achieved in seven of nine patients after the single dose and in seven of eight patients at steady-state. For those patients whose cultures grew Pseudomonas spp, only one patient after the single dose and one patient at steady-state achieved a C(max)/MIC ratio of >8. A significant association was noted between dose and survival, and a trend was observed with patients weighing ≤ 60 kg (who received 50,000 IU/kg/day instead of 6 MIU/day for those >60 kg) having an increased mortality. CONCLUSION: The pharmacokinetic parameters of colistin were comparable to those reported in previous studies in critically ill patients. However, the recommended dose may be inadequate to maintain the C(max)/MIC ratio to an optimal level-at least in patients infected with Pseudomonas spp. The dose recommendation should be based only on creatinine clearance and not body weight.
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Acinetobacter/efectos de los fármacos , Antibacterianos/farmacocinética , Colistina/farmacocinética , Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Pseudomonas/efectos de los fármacos , Acinetobacter/clasificación , Acinetobacter/aislamiento & purificación , Adolescente , Adulto , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/sangre , Colistina/administración & dosificación , Colistina/efectos adversos , Colistina/análogos & derivados , Colistina/sangre , Femenino , Infecciones por Bacterias Gramnegativas/sangre , Infecciones por Bacterias Gramnegativas/complicaciones , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , India , Infusiones Intravenosas , Unidades de Cuidados Intensivos , Riñón/fisiopatología , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Masculino , Staphylococcus aureus Resistente a Meticilina/clasificación , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Pseudomonas/clasificación , Pseudomonas/aislamiento & purificación , Insuficiencia Renal/complicaciones , Insuficiencia Renal/fisiopatología , Centros de Atención Terciaria , Adulto JovenRESUMEN
OBJECTIVES: Studies on antimalarial kinetics in children or adults who are undernourished or malnourished are both limited and have yielded conflicting results. The present study was carried out with the objectives of evaluating the pharmacokinetics of single dose chloroquine and its metabolite desethylchloroquine in children who were undernourished and compare them with children who were normally nourished. METHODS: Children of either gender between the ages of 5 and 12 years, smear positive for P. vivax malaria and classified either as well nourished or undernourished were included. Undernourishment was adjudged based on the Indian Academy of Pediatrics (IAP) classification of protein energy malnutrition [PEM] which in turn was based on Khadilkar's growth charts. All participants received 10 mg/kg on the first day followed by 10 mg/kg on Day 2 and 5 mg/kg on Day 3 along with supportive treatment. Blood samples for the levels of chloroquine [CQ] and desethylchloroquine [DECQ] were collected at 0, 0.5, 1, 2 4, 8, 12, 24, 48, 72 hours and 14 days after the first dose and levels assessed by High Performance Liquid Chromatography. RESULTS: A total of 12 children who were normally nourished and 13 who were undernourished were studied. Wide inter-individual variability was seen in the levels of both drug and metabolite in both groups of patients. However, the differences in Cmax, AUC 0-inf, Clearance, half life and Vd between the two groups were not significantly different. DISCUSSION: Our results indicate that dosage requirement is unlikely to be needed for chloroquine in undernourished children with uncomplicated P. vivax malaria.
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Antimaláricos/farmacocinética , Trastornos de la Nutrición del Niño/metabolismo , Cloroquina/farmacocinética , Malaria Vivax/metabolismo , Antimaláricos/administración & dosificación , Antimaláricos/sangre , Antimaláricos/uso terapéutico , Niño , Trastornos de la Nutrición del Niño/sangre , Trastornos de la Nutrición del Niño/tratamiento farmacológico , Preescolar , Cloroquina/administración & dosificación , Cloroquina/análogos & derivados , Cloroquina/sangre , Cloroquina/uso terapéutico , Femenino , Humanos , Malaria Vivax/sangre , Malaria Vivax/tratamiento farmacológico , MasculinoRESUMEN
BACKGROUND: Growth factors have long been known as an effective treatment for facial wrinkles. We developed growth factor concentrate (GFC) from the platelets and evaluated their clinical outcome in nasolabial folds. AIMS AND OBJECTIVES: We evaluated safety and efficacy of autologous GFC on patients with nasolabial folds. MATERIALS AND METHODS: Study was conducted on 80 patients for nasolabial folds in two groups. Group I (20) received bilateral single injection of GFC and group II (60) received single injection of GFC on the right side of the face and platelet-rich plasma (PRP) on the left side of the face. Severity of nasolabial folds was determined at the baseline and 3 months of follow-up visits based on wrinkle severity rating scale (WSRS), Global aesthetic improvement scale (GAIS) and atlas photographic grading at rest and at full smile. Objective clinical assessment and subjective satisfaction scale was determined for overall improvement at the end of the study. RESULTS: In group I, 2 subjects showed improvement after GFC treatment with the score of 3.1-4 (76-100%), 3 subjects with the score of 2.1-3 (51-75%), 14 with the score of 1.1-2 (26-50%) and 1 subject with the score of 0-1 (<25%) at the end of study. In group II, 51 subjects were evaluated at the end of study where, 34 (66%) showed superior improvements after GFC, 6 (11%) patients showed similar improvement on both side of the face, 10 (19.6%) patients showed no noticeable improvement on the either side of the face and only 1 patient (1.96%) showed superior improvement for PRP at the end of the study. Overall improvement score analysis showed that GFC was significantly superior to PRP (P < 0.001). CONCLUSION: Present study is a strong evidence to support the use of GFC for nasolabial folds. The results showed that the single application of GFC is highly effective and safe.
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BACKGROUND: Cytochrome P450 2D6 (CYP2D6) metabolizes around 25% of the drugs used in therapeutics and different polymorphisms have been identified in various populations. This study aimed at finding the prevalence of CYP2D6 polymorphisms using dextromethorphan as a probe drug. MATERIALS AND METHODS: Healthy participants were administered 60 mg dextromethorphan after an overnight fast and 5 ml of blood was collected 3 h postdose. A validated laboratory method was used to measure both dextromethorphan and its active metabolite, dextrorphan from plasma. Metabolic ratio (MR) of dextromethorphan to dextrorphan was calculated for each of the participants. Probit analysis was done and antimode was defined. Individuals with log MR equal to or higher than the antimode were classified as poor metabolizers (PMs) and those with values less than antimode were categorized as extensive metabolizers (EMs). RESULTS: Data from a total of 149 participants were evaluated and the median (range) of MR was 0.25 (0.03-3.01). The polynomial equation obtained in probit analysis gave an antimode for MR of 1.39. Five (3.36%) participants were PMs and 144 (96.64%) were found to be EMs. One participant had reported mild drowsiness 2 h postdose that subsided spontaneously without any intervention. CONCLUSION: The prevalence of CYP2D6 polymorphism in Western Indian population is low (3.36%) and is similar to other populations.
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Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Dextrometorfano/farmacocinética , Población Blanca/genética , Adolescente , Adulto , Dextrometorfano/sangre , Dextrorfano/sangre , Femenino , Humanos , India , Masculino , Fenotipo , Polimorfismo Genético , Adulto JovenRESUMEN
AIM: The pharmacokinetics of primaquine has not been studied in special populations. Being a basic compound, preferential binding to alpha-1 acid glycoprotein and substrate for P-glycoprotein, may predispose the drug for an altered pharmacokinetics in states of renal dysfunction. This study attempts to evaluate the pharmacokinetics of a single oral dose (15 mg) of primaquine in severely impaired renal function and end stage renal dysfunction patients compared to healthy participants. MATERIALS AND METHODS: Twelve patients each with chronic kidney disease classified as either Stage IV or V (not on dialysis) were recruited. Data from 12 healthy participants was used as concurrent controls. Serial blood collections were performed following a single dose 15 mg Primaquine orally. Primaquine concentrations were measured in the plasma using a validated HPLC method. RESULTS: The Cmax [median (range) in ng/ml] was 29.3 (14.6-104.3), 40.3 (14.8 - 78.6), and 49.8 (15 - 169.6) and the tmax [median (range) in hours] was 3.0 (1.0- 6.0), 2.0 (1.5 - 8) and 2.0 (1.0 - 4.0) for healthy and stage IV, V (not on dialysis) CKD participants, respectively. No statistically significant difference was observed in any of the pharmacokinetic parameters between healthy, stage IV and V CKD participants. CONCLUSION: Pharmacokinetics of single oral dose primaquine (15 mg) does not appear to be altered in patients with severely impaired renal function and end stage renal dysfunction. A change in dose or frequency of the drug administration perhaps may not be required in this population.
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Antimaláricos/farmacocinética , Primaquina/farmacocinética , Insuficiencia Renal Crónica/metabolismo , Adulto , Antimaláricos/administración & dosificación , Antimaláricos/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Primaquina/administración & dosificación , Primaquina/sangre , Adulto JovenRESUMEN
The potential of Compritol(®)888 ATO as a release modifier to retard the release of highly water soluble drug, metoprolol succinate (MPL) was exploited. Different ratios of Compritol(®)888 ATO versus MPL were utilized and the effect of various formulation methods was evaluated to sustain the release of MPL. MPL: Compritol(®)888 ATO in 1:2 ratio could successfully retard the release of MPL. Melt granulation method "as hot process" was found to be effective when compared to direct compression and wet granulation. The in vitro release characteristics of tablets were studied in pH 6.8 phosphate buffer at 50 rpm using USP Type II apparatus. Formulation F7 retarded MPL release with ~90% release after 20 h. Stability studies showed no significant difference (f2>50) in MPL release profile after three months of storage period at 25 ± 2°C/60 ± 5% RH and 40 ± 2°C/75 ± 5% RH. The bioavailability of sustained release tablets, F7 was compared with commercially available tablets, MetXL50 in 12 healthy human volunteers in a crossover design. Plasma concentration of MPL was determined using HPLC with fluorescence detector. IVIVC correlation was obtained by deconvoluting the plasma concentration-time curve using a model independent Wagner-Nelson method. Correlations of fraction of drug dissolved in vitro and fraction of drug absorbed in vivo displayed a significant linear relationship for sustained release tablets of MPL.