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ABSTRACT: This study was undertaken to compare the bioavailability and pharmacokinetic properties of 3 marketed product of metformin (CAS 1115-70-4) extended/sustained release formulation in Indian male volunteers. Study was designed as an open-label, randomized, 3-treatment, single-dose, crossover, bioavailability study comparing 3 marketed brands of 500 mg metformin extended/sustained release tablets in 18 healthy human male volunteers under fed condition. A single oral dose of 500 mg metformin sustained release products, test A (Glycomet SR), test B (Bigomet SR) and extended release reference product was administered as per computer generated randomization schedule during 3 period of the study having 7 days of washout period. A liquid Chromatography mass spectroscopy method for the determination of metformin in human plasma was developed and validated using metformin-D6 as an internal standard. A noncompartment pharmacokinetic method was employed to determine the pharmacokinetic parameters (Cmax, Tmax, AUC0-t, AUC0-∞ and t½) of metformin using WinNonlin-Node 4.0 software. Cmax, AUC0-t and AUC0-∞ were used to test for bioequivalence after log transformation of plasma data. The predetermined regulatory range of 90% CI for bioequivalence was 0.80 to 1.25. The 90% confidence intervals for log transformed data for Cmax, AUC0-t and AUC0-∞ for test A vs. reference were 82.11-98.91, 86.29-102.17 and 86.34-102.59 respectively whereas for test B vs. reference were 104.39-125.76, 94.78-112.22 and 92.85-110.33 respectively. The results of this study suggest that the test A was bioequivalent to reference product, whereas test B was not as per regulatory defined criteria.
Arzneimittel-Forschung 01/2012; 62(1):22-6. · 0.72 Impact Factor
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ABSTRACT: To find out the pharmacokinetic (PK) and pharmacodynamic (PD) parameters for assessing the bioequivalence of three marketed products. To study the relationship between the pharmacokinetics of gliclazide and pharmacodynamic effect in healthy male volunteers.
This was an open label, balanced, randomized, 3-treatment, 3-sequence, 3 period, single-dose, cross-over bioavailability study in which 18 healthy adults were randomized to receive gliclazide 80 mg with 7 days wash out between treatments. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. Pharmacokinetic parameters like t(max), C(max), AUC(0-t), AUC(0-∞), AUC(0-t) / AUC(0-∞) and t(1/2) and pharmacodynamic parameters like maximum effect (minimum glucose level in the body, C(minglu)), time to minimum glucose level in the body (T(cminglu)) and partial AUC were calculated for all the products.
The values for mean ± SD for age, height and weight of the volunteers were 28.00 ± 22.68, 165.78 ± 5.56 and 56.78 ± 13.37 respectively. There were total 4 withdrawn subjects and 1 drop out. Within batch accuracy of the method were in the range of 95.5 - 101.7%, 99.1 - 106.1% and 96.2 - 104.2% for three consecutive batches. The 90% CI for log transformed data of the PK and PD were within the acceptance range of 80.0 - 125.0%.
This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its hypoglycemic effect. The test products A & B compared to reference product R were bioequivalent on the basis of pharmacokinetic and pharmacodynamic parameters. Finally it is recommended that the more costly product R can be safely switched with less costly products i.e. A and B.
International journal of clinical pharmacology and therapeutics 07/2011; 49(7):444-50. · 1.18 Impact Factor
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ABSTRACT: In this open-label, balanced, randomized, placebo-controlled, parallel study, healthy male volunteers were randomly divided into two groups. Each group received either a single oral dose of rosuvastatin 20 mg or placebo. Estimations were done at predose on day 1 of dosing (baseline) and 24 h postdose after days 7 and 14. Serum cortisol and serum lipid levels were estimated using enzyme-linked immunosorbent assay kits and serum mevalonic acid (MVA) levels were measured using validated liquid chromatography-tandem mass spectrometry method. Rosuvastatin produced a statistically significant (P < 0.05) decrease in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides. However, the increase in high-density lipoprotein cholesterol and decrease in cortisol and MVA were not statistically significant when compared to the placebo-treated group. The study showed that rosuvastatin at a dose of 20 mg/day for a period of 14 days was very potent as cholesterol-lowering agent, without any significant change in serum cortisol level in the healthy Indian male population.
AAPS PharmSciTech 03/2010; 11(1):425-32. · 1.43 Impact Factor
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AAPS PharmSciTech 01/2010; 1:425-432. · 1.43 Impact Factor
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Letters in Drug Design & Discovery 01/2009; 6:629-636. · 0.87 Impact Factor
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ABSTRACT: Soluble fibre supplements are recommended to reduce the levels of low-density lipoprotein cholesterol (LDL-C). Limited information exists on the interaction between fibre and hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). The purpose of the present study was to evaluate the per se effect of psyllium (10 g/day) and lovastatin (20 mg/day) alone and in combination on serum lipids in normal human volunteers.
In a 4-week open label, randomised, parallel study, subjects were randomised to receive 20 mg of lovastatin, 10 g of psyllium or 20 mg of lovastatin plus 10 g of psyllium in evening daily. Levels of total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), TC/LDL-C ratio, LDL-C/HDL-C ratio and triglycerides were determined after 1, 2, 3 and 4 weeks of treatment.
The study group comprised 36 adult, male subjects. All treatments were well tolerated, and after 4 weeks the mean LDL-C, TC and TG levels in the group receiving 20 mg of lovastatin plus 10 g of psyllium fell by 30.88%, 26.88% and 26.21% from baseline, compared with 24.78%, 19.55% and 32.88% in the group receiving 20 mg of lovastatin and 3.58%, 2.90% and 10.95% in the group receiving 10 g of psyllium respectively. Although additive effect was observed in the group receiving combination compared with group receiving lovastatin, the observed difference was not statistically significant. No significant changes from baseline in HDL-C levels occurred.
Psyllium soluble fibre should be considered as a safe and well-tolerated dietary supplement option to enhance cholesterol lowering.
International Journal of Clinical Practice 12/2007; 61(11):1812-8. · 2.41 Impact Factor
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ABSTRACT: This randomized, open-label, balanced, five-treatment, five-period, five-sequence, single-dose and crossover pharmacokinetic study assessed the effect of different types of food on the bioavailability of cefaclor in 18 healthy male volunteers. A single dose of cefaclor, 250-mg capsule was administered at five occasions: after overnight fasting, after two vegetarian (high-fat and low-fat) diets and two non-vegetarian (high-fat and low-fat) diets. Serial blood samples were collected upto 8 h post dose. Serum cefaclor concentrations were determined by a validated HPLC method. AUC values were not significantly affected by food intake, but the T(max) was prolonged and C(max) was decreased, depending on the type of meal. The non-vegetarian diets affected the rate of absorption of cefaclor more than the vegetarian diets. The least decrease in C(max) was produced by low-fat vegetarian diet, while the maximum decrease was produced by high-fat non-vegetarian diet. The results of this study indicate that while the rate of absorption of cefaclor is significantly decreased, the extent of absorption and the rate of elimination are not significantly decreased in the presence of food. As compared to high-fat non-vegetarian diet, the time above MIC50 concentration was significantly increased by low-fat vegetarian diet. The implications of these findings for the large vegetarian Indian population are considerable.
European Journal of Drug Metabolism and Pharmacokinetics 28(3):185-90. · 0.36 Impact Factor
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ABSTRACT: This randomized open-label single-dose crossover pharmacokinetic study was carried out to assess the effect of different diets on the bioavailability of loracarbef in 24 healthy male volunteers. A single dose of loracarbef in 200-mg tablet form was administered at 5 different times: after overnight fasting, after two vegetarian (high-fat and low-fat) diets, and following two non-vegetarian (high-fat and low-fat) diets. Serial blood samples were collected up to 10 h post-dose. Serum loracarbef concentrations were determined by a validated high performance liquid chromatographic (HPLC) method. Area under curve (AUC) values were significantly affected only by non-vegetarian diets; however the time to reach maximum serum concentration (Tmax) was prolonged and the maximum serum concentration (Cmax was decreased by all types of meals. The non-vegetarian diets affected the rate of absorption of loracarbef more than the vegetarian diets. The lowest decrease in Cmax was produced by the high-fat vegetarian diet, while the maximum was produced by the low-fat non-vegetarian diet. The results of this study indicate that while the rate of loracarbef absorption is significantly decreased by all diets, the extent of absorption is only reduced significantly by the non-vegetarian diets. The rate of elimination (k(el)) was not found to be significantly decreased by any of the diets. As compared to the high-fat non-vegetarian diet, the time beyond minimum inhibitory concentration (MIC90) concentration was significantly increased by the high-fat vegetarian diet. The implications of these findings for the large Indian vegetarian population are considerable.
European Journal of Drug Metabolism and Pharmacokinetics 32(4):205-11. · 0.36 Impact Factor
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ABSTRACT: This randomized, six-treatment, six-period, six sequence, single dose, crossover pharmacokinetic study assessed the effect of different types of food on the bioavailability of 500-mg cefaclor extended release tablet in 23 healthy male volunteers. A single dose of cefaclor extended release 500-mg tablet was administered at six occasions: after overnight fasting, after two vegetarian (high-fat and low-fat), two non-vegetarian (high-fat and low-fat) and rice diets. Serial blood samples were collected up to 12 h after dose. Serum cefaclor concentrations were determined by a validated HPLC method. An almost equivalent increase in both Cmax and AUC was observed with both high-fat non-vegetarian and low-fat vegetarian breakfasts. However, when MIC90 values, a pharmacodynamic end-point were compared, the low-fat vegetarian diet fared better than the high-fat non-vegetarian diet. The results obtained favor low-fat vegetarian diet (breakfast) to be taken with cefaclor extended release tablet to achieve maximum benefit in terms of clinical efficacy.
European Journal of Drug Metabolism and Pharmacokinetics 29(2):125-32. · 0.36 Impact Factor
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ABSTRACT: Objective: To determine the bioequivalence of two marketed test formulations (A, B) as compared to a reference formulation (R) of slow release theophylline in healthy volunteers. Material and Methods: The study was conducted as an open label, balanced, randomized, three-treatment, three-period, three-sequence single-dose crossover study to determine the bioequivalence of Phylobid 200 mg SR tablets (A) and Theobid 200 mg SR tablets (B) as compared to Theostan CR 200 mg capsule (R) under fasting conditions. A group of 12 healthy, adult, male human subjects participated in this study. The bioavailability was compared using pharmacokinetic parameters Cmax, Tmax, AUC0-t, and AUC0-∞. Moreover, the 90% confidence interval (CI) for the ratio of logarithmic transformed Cmax, AUC0-t and AUC0-∞ was also used to determine bioequivalence. A washout period of seven days was kept between each study period. Serial blood samples were collected at 0, 0.5, 2, 3, 4, 6, 8, 10, 12, 15, 18, 21 and 24 h during each study. Results: The 90% CI for the log transformed data forCmax, AUC0-t, and AUC0-∞ for both the test products fell outside the prescribed limits of bioequivalence for narrow therapeutic index drugs i.e. 90-111%. The T/R (test/reference) ratio of product A was quite close to the prescribed limits of bioequivalence (95-105%), while for product B the T/R ratio was not satisfactory. Conclusions: None of the test products of theophylline were bioequivalent to the reference product. The finding is of special significance since substitution of one brand of theophylline, a drug with a narrow therapeutic index, with another brand may result in sub-therapeutic response in patients.
Indian Journal of Pharmacology (ISSN: 0253-7613) Vol 36 Num 1.
