Ji-Seok Yoo

Pharmacokinetic properties and bioequivalence of candesartan cilexetil in Korean healthy volunteers.

Candesartan is a long-acting and selective nonpeptide AT1 subtype angiotensin II receptor antagonist. The aim of this study was to compare the pharmacokinetics and to evaluate the bioequivalence of two candesartan cilexetil 16 mg formulations. Forty healthy volunteers were randomly assigned into two groups. After a single dose of 16 mg candesartan cilexetil oral administration, blood samples were collected at specific time intervals from 0–36 h. The plasma concentrations of candesartan cilexetil were determined by LC-MS/MS. The pharmacokinetic parameters such as AUClast, AUCinf and Cmax were calculated and the 90% confidence intervals of the ratio (test/reference) pharmacokinetic parameters were obtained by analysis of variance on logarithmically transformed data. The mean for AUClast in the reference and the test drug were 1530.1 ± 434.6 and 1315.7 ± 368.6 ng·h/mL. The mean for AUCinf in the reference and the test drug were 1670.0 ± 454.5 and 1441.2 ± 397.8 ng·h/mL. The mean value for Cmax in the reference and the test drug was 142.6 ± 41.0 and 134.9 ± 41.4 ng/mL. The 90% confidence intervals for the AUClast, AUCinf and Cmax were in the range of log 0.81–log 0.91, log 0.81–log 0.91 and log 0.88–log1.01, respectively. No adverse events were reported by subjects or found on analysis of vital signs or laboratory tests. This single dose study found that the test and reference products met the regulatory criteria for bioequivalence in these health volunteers. Both formulations were safe and well tolerated in 16 mg of candesartan cilexetil hydrochloride.

An Assessment of the Pharmacokinetics of a Sustained-release Formulation of a Tramadol/Acetaminophen Combination in Healthy Subjects

PURPOSE To provide consistent pain relief and improve convenient sustained release (SR), a fixed-dose combination tramadol/acetaminophen tablet was formulated. This study aimed to evaluate the pharmacokinetic profiles of an SR 75-mg tramadol/650-mg acetaminophen formulation after a single dose compared with an immediate release (IR) 37.5-mg tramadol/325-mg acetaminophen formulation after 2 doses and at steady state and to assess the effect of food on the pharmacokinetic SR formulation profile after a single dose. METHODS Two clinical trials were conducted: (1) an open-label, randomized, 3-period, 3-treatment, crossover study to assess the pharmacokinetic SR (one 75-mg tramadol/650-mg acetaminophen combination tablet) formulation profiles after a single dose and IR (one 37.5-mg tramadol/325-mg acetaminophen combination tablet q6h for 2 doses) formulation profiles after 2 doses and the effect of food intake on healthy male subjects and (2) an open, randomized, 2-period, 2-treatment multiple dose crossover study to evaluate the steady-state pharmacokinetic SR and IR formulation profiles. Safety assessments were performed. FINDINGS Forty-three subjects completed each study protocol. The SR combination tramadol/acetaminophen formulation was clinically and statistically equivalent to the IR combination formulation in the fasting state. When tramadol and acetaminophen tablets were administered with food, the time to peak plasma concentrations and the tramadol/acetaminophen absorption were unaffected. There was no serious adverse event reported. IMPLICATIONS The SR combination tramadol/acetaminophen tablet exhibited similar exposure and absorption rates compared with those of the IR formulation of tramadol, O-desmethyltramadol, and acetaminophen. The SR formulation may be more convenient for patients and has the potential to enhance compliance and pain control. ClinicalTrials.gov identifier: NCT01880125.