ABSTRACT
Objective:To optimize the clinical dosage regimen of amoxicillin and clavulanate potassium extended release ( ER) tablets based on the PK/PD parameters. Methods:Totally 30 healthy subjects ( half male and half female) were randomly divided into three groups, and orally administered the ER tablets respectively under fasting condition, before the meal and after the meal, and the optimal administration time was determined by comparing the pharmacokinetic characteristics. The subjects in the three groups were ad-ministered the ER tablets respectively at low, medium and high dosage, and the optimal dosage and dosing interval were determined based on the PK/PD parameters. Results:Under fasting condition, the AUC of amoxicillin [(32.2 ±15.0) μg·h·ml-1] was sig-nificantly lower than that before the meal [(41.7 ±1.92) μg·h·ml-1] and that after the meal [(42.6 ±17.7) μg·h·ml-1]. In contrast, the AUC of clavulanate acid after the meal [(1.89 ±0.54) μg·h·ml-1] was significantly lower than that under fasting condition [(2.55 ±0.76) μg·h·ml-1] and that before the meal [(2.58 ±0.76) μg·h·ml-1] (P MIC) in 12 h was 5. 5, 7 and 10 h, and the percentage was 46%, 58% and 83%, respectively, and T> MIC in 12 h was 4. 5, 6 and 8 h, and the percentage was 38%, 50% and 67%, re-spectively when MIC was 4. 0μg·ml-1 . Conclusion:It is suggested that amoxicillin and clavulanate potassium ER tablets be taken at the start of a standard meal, 2 tablets per time, twice daily, which is sufficient to achieve T> MIC of 40% -50%.
ABSTRACT
Objective To establish an analytical method for assessing acetylcysteine in human plasma and study the relative bioavailability and bioequivalence of acetylcysteine granules in Chinese healthy volunteers. Methods In the randomized crossover study, 24 healthy male volunteers received a single oral dose of 0. 6 g test acetylcysteine granules, reference acetylcysteine granules or no medication. The plasma concentration of acetylcysteine was determined by LC-MS/MS. Pharmacokinetic parameters were calculated and bioequivalence of two preparations were evaluated by DAS3. 0 software. Results The main pharmacokinetic parameters of the test and reference preparations were as follows:AUC0→t was (8 547. 64± 2 860.04) and (8 783.07±4 042. 10) μg·h·L-1, respectively; AUC0→∞ was (9 481. 64±3 444. 76) and (9 540. 51± 4 239. 30) μg·h·L-1, respectively;Cmax was (1 994. 39±726. 42) and (2 090. 27±885. 46) μg·L-1, respectively;tmax was (1.18±0. 60) and (1. 13±0. 53) h, respectively; t1/2 was (8. 60±3. 76) and (7. 75±5. 01) h, respectively. The relative bioavailability F0→t and F0→∞ was ( 107. 0 ± 43. 3 )% and ( 106. 5 ± 40. 1 )%, respectively. Conclusion The results of statistical analysis indicate that the test and reference formulations are bioequivalent.