Subject(s)
Gastrointestinal Tract/metabolism , Itraconazole/pharmacokinetics , Models, Biological , Administration, Oral , Antifungal Agents/administration & dosage , Antifungal Agents/blood , Antifungal Agents/pharmacokinetics , Biological Availability , Clinical Trials as Topic , Humans , Itraconazole/administration & dosage , Itraconazole/blood , Male , Metabolic Clearance Rate , Time FactorsABSTRACT
AIMS: To investigate the effects of antacid suspension on oral absorption of itraconazole. METHODS: A randomized, open-labelled, two-period, crossover study with a 1-week washout period was conducted in 12 healthy Thai male volunteers. The participants were allocated in either treatment A or B in the first period. In treatment A, the volunteers were orally administered with 200 mg of itraconazole alone. In treatment B, the volunteers were administered orally with 200 mg of itraconazole co-administered with antacid suspension. Serial serum samples were collected over the period of 24 h and subsequently analysed by using a validated high-pressure liquid chromatographic method with ultraviolet detection. Pharmacokinetic parameters were determined by non-compartmental analysis. RESULTS: Time to reach maximal concentration (Tmax), maximal concentration (Cmax) and area under the curve (AUC0-infinity) were markedly decreased in antacid-treated group. Tmax for treatment A was 3.0 +/- 0.4 and 5.1 +/- 2.7 h for treatment B. Cmax and AUC0-infinity of treatments A and B were 146.3 +/- 70.5 vs. 43.6 +/- 16.9 (ng/mL) and 1928.5 +/- 1114.6 vs. 654.8 +/- 452.2 (ng x h/mL) respectively. 90% Confidence interval (90% CI) of Cmax and AUC0--infinity were 24.1-42.1 and 16.2-65.9 respectively. CONCLUSIONS: Rate and extent of itraconazole oral absorption were markedly decreased by concurrent use of antacid suspension. Hence, co-administration of itraconazole and antacid suspension should be avoided.
Subject(s)
Aluminum Hydroxide/pharmacology , Antacids/pharmacology , Antifungal Agents/pharmacokinetics , Itraconazole/pharmacokinetics , Magnesium Hydroxide/pharmacology , Adolescent , Adult , Area Under Curve , Biological Availability , Cross-Over Studies , Drug Antagonism , Drug Combinations , Humans , Intestinal Absorption , Male , Middle Aged , SuspensionsABSTRACT
The objective of this study was to assess average bioequivalence of two immediate released tablet formulations of 500-mg clarithromycin tablets in 24 healthy Thai male volunteers. In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500-mg clarithromycin tablet. Plasma samples were collected over a 24-hour period after oral administration and were analyzed by using a validated method using high performance liquid chromatography with electrochemical detection. Pharmacokinetic parameters were determined by using noncompartmental analysis. The time to reach the maximal concentration (tmax, h), the peak concentration (Cmax, ng/mL), and the area under the curve (AUC0-infinity, ng x h/mL) of the Reference and Test formulations were 2.0 +/- 0.8 vs. 2.2 +/- 0.9, 2793 +/- 1338 vs. 2642 +/- 1344, and 17912 +/- 7360 vs. 17660 +/- 7992, respectively. Relative bioavailability was 0.99. The 90% confidence interval of Cmax and AUC0-infinity were 82.6-112.1% and 84.7-112.0%. Bioequivalence between the Test and Reference formulation can be concluded.
Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Clarithromycin/pharmacokinetics , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/adverse effects , Area Under Curve , Biological Availability , Chromatography, High Pressure Liquid , Clarithromycin/administration & dosage , Clarithromycin/adverse effects , Cross-Over Studies , Half-Life , Humans , Male , Solubility , Tablets , Therapeutic EquivalencyABSTRACT
OBJECTIVE: To evaluate the average bioequivalence of two formulations of 500 mg clarithromycin tablets in 24 healthy Thai male volunteers. METHODS: In a randomized, single dose, fasting state, two-period, crossover study design with a 1-week washout period, each subject received a 500 mg clarithromycin tablet. Plasma samples were collected over a 24-h period after administration and were analysed by using a validated HPLC-ECD method. Pharmacokinetic parameters were determined by using non-compartmental analysis. RESULTS: The time to reach the maximal concentration (tmax, h), the peak concentration (Cmax, ng/mL) and the area under the curve (AUC0- infinity, ng h/mL) of the Reference and Test formulations were 2.0 +/- 0.9 vs. 1.8 +/- 1.1, 3018 +/- 841 vs. 3014 +/- 752 and 23142 +/- 7348 vs. 22810 +/- 6027, respectively. The 90% confidence interval of Cmax and AUC0- infinity were 90.6-109.4 and 89.6-110.1%. CONCLUSION: Bioequivalence between the Test and Reference formulation can be concluded.
