Identical pattern of highly variable absorption of clavulanic acid from four different oral formulations of co-amoxiclav in healthy subjects.
The aims of this investigation were to calculate the pharmacokinetic parameters of amoxicillin and clavulanic acid, and to identify parameters that may affect their observed differences in absorption. Data were obtained from plasma concentration-time curves from four different open, randomized, two-treatment, two-period, two-sequence, crossover Phase I bioequivalence studies, with the following co-amoxiclav formulations: tablets 250/125, 500/125 and 875/125 mg, or 10 mL of an oral suspension 250/62.5 mg per 5 mL. Data from 144 subjects and 288 drug administrations were available for evaluation. After a 125 mg clavulanic acid dose (administered as potassium clavulanate) for all four different formulations, the clavulanic acid AUC(t) data ranged from 1.5 to 8 mg.h/L, varying by a factor of 5. The absorption of clavulanic acid was not related to the absorption of amoxicillin, or demographic factors, and we were unable to identify the reasons for the large variability in the absorption of clavulanic acid. We conclude that the absorption of clavulanic acid, after oral administration, is highly variable and may vary over a five-fold range between patients.
Vree
Tom B
TB
Institute for Anaesthesiology, University Medical Centre Sint Radboud, PO Box 9101, 6500 HB Nijmegen. T.Vree@anes.azn.nl
Dammers
Erik
E
Exler
Peter S
PS
D000328:Adult; D000658:Amoxicillin / Q000097:blood; D019980:Amoxicillin-Potassium Clavulanate Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid; D019818:Clavulanic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D013058:Mass Spectrometry
D000900:Anti-Bacterial Agents; D019818:Clavulanic Acid; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin