Pharmacokinetic properties of isosorbide-5-mononitrate under fasting and fed conditions in healthy male subjects.

OBJECTIVE: This study was performed to compare the pharmacokinetic properties and relative bioavailability of two isosorbide-5-mononitrate (5-ISMN) sustained-release drugs in healthy Korean subjects under fasting and fed conditions. METHODS: A total of 60 healthy volunteers (30 each in the fasting and fed arms of the study) were enrolled in the study and were randomized to treatment. After the administration of a single dose of one of the investigational products, blood samples were collected at specific time intervals from 0 to 36 hours. The plasma concentrations of 5-ISMN were measured by LC-MS/MS. The pharmacokinetic parameters were calculated, and the 90% confidence intervals (CIs) of the geometric mean ratio (test/reference) of the parameters were obtained by analysis of variance on logarithmically transformed data. RESULTS: The corresponding 90% CIs of AUClast and Cmax for the test/reference geometric mean ratio were 90.75 - 98.44% and 92.28 - 98.33%, respectively, under fasting conditions. In the fed state study, the 90% CIs for the geometric mean ratio of test to reference drugs were 94.79 - 103.33% for AUClast and 99.86 - 108.02% for Cmax. CONCLUSION: The test product is equivalent to the reference product in subjects under fasting and fed conditions within the Korean regulatory bioequivalence criteria. Both formulations were safe and well tolerated, and there were no noteworthy differences in the safety profiles between the test and reference drugs.

Pharmacokinetic comparison study of a combination containing 500 mg of Naproxen and 20 mg of Esomeprazole: a randomized, single-dose, 2-way crossover, open-label study in healthy Korean men.

PURPOSE: Nonsteroidal anti-inflammatory drugs have been used for analgesic, anti-inflammatory, and antithrombotic effects, but they carry a risk of major gastrointestinal damage. This risk can be greatly reduced by the coadministration of inhibitors of gastric acid secretion, such as proton pump inhibitors. This study was performed for the subsequent marketing of a combination drug that contained 500 mg of naproxen and 20 mg of esomeprazole in Korea. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy men. METHODS: A total of 60 healthy men were enrolled in this single-dose, randomized, open-label, 2-period, 2-sequence, crossover study. During each period, men received a combination of 500 mg of naproxen and 20 mg of esomeprazole for test or reference, and between each period, there was a 1-week washout period. Blood samples were obtained 21 times throughout each period before dosing and 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, 12, 24, 48, and 72 hours after oral administration. Plasma concentrations were determined using LC-MS/MS. The pharmacokinetic parameters, including Cmax, AUC0-t, AUC0-∞, and Tmax, were measured, and all treatment-emergent adverse events and their associations with the study medications were recorded throughout the entire study. FINDINGS: A total of 59 men completed the study. No significant differences were found in the prevalence of AEs between the 2 formulations. In addition, there were no serious or unexpected AEs during the study. Both formulations had very similar Cmax, AUC, and t½ values, but the Tmax of naproxen appeared earlier in the test formulation than in the reference formulation and that of esomeprazole appeared later in the test formulation than in the reference formulation. IMPLICATIONS: This study suggests that the test and reference formulations of a combination of 500 mg of naproxen and 20 mg of esomeprazole are bioequivalent in the extent of absorption and peak concentration. We anticipate that the test formulation will treat those who need relief from pain and inflammation and will decrease the risk of developing gastric ulcers. cris.nih.go.kr identifier: KCT0001117.

Pharmacokinetic properties and bioequivalence of olmesartan medoxomil/hydrochlorothiazide in healthy Korean male subjects.

UNLABELLED: Olmesartan medoxomil inhibits the vasoconstrictor effects of angiotensin II. Hydrochlorothiazide (HCTZ) promotes sodium excretion, resulting in a reduction of plasma volume and peripheral resistance. A combination of these agents is known to have a greater effect for the treatment of hypertension than monotherapy with either one of these components. OBJECTIVE: To assess bioequivalence between fixed-dose combination of olmesartan medoxomil and hydrochlorothiazide (HCTZ) in healthy Korean subjects. METHODS: 40 healthy Korean volunteers were randomized into two groups. After administration of a single dose of investigational products, blood samples were collected before study drug administration (baseline) and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, and 36 hours after study drug administration. The plasma concentrations of olmesartan and HCTZ were measured by LC-MS/MS. The pharmacokinetic parameters were calculated, and the 90% confidence intervals (CIs) of the geometric mean ratio (test/reference) of the parameters were obtained by analysis of variance (ANOVA) on logarithmically transformed data. RESULTS: The corresponding 90% CIs for the geometric mean ratio of the test to reference drugs were 0.93 - 1.04, 0.93 - 1.04, and 0.95 - 1.10. For HCTZ treatments, the 90% CIs for the geometric mean ratio of test to reference drugs were 0.95 - 1.03 for AUClast, 0.96 - 1.03 for AUC∞, and 0.89 - 1.04 for Cmax. CONCLUSION: This study demonstrated that the test and reference products met the regulatory criteria assuming bioequivalence. Both formulations were safe and well tolerated, and there were no noteworthy differences in the safety profiles of the test and reference drugs.