Pharmacokinetic studies of amoxicillin, potassium clavulanate and their combination

Witkowski, Grzegorz; Lode, H.; Höffken, G.; Koeppe, P.

doi:10.1007/bf02019714

Cited by 18 publications

(14 citation statements)

References 13 publications

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“…Serum amoxicillin concentration found in this study is comparable to levels previously reported [18][19][20][21]; however, what is remarkable here is the high prevalence of children with low plasma levels. Although delays in collecting blood samples cannot be excluded, we ascribe it to a low compliance of the patient to the chemoprophylaxis protocol (i.e.…”

Section: Discussionsupporting

confidence: 90%

“…Department of ''Amedeo Avogadro'' University of Eastern Piedmont in Novara for elective tonsillectomy. All tonsils were removed by cold dissection tonsillectomy, with a mean surgery time of 20 min (range [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30]. Previously, patients were treated with 3 doses of amoxicillinclavulanic acid given orally the day before plus a further dose given 2 h before admittance into the operating theatre.…”

Section: Subjects and Samplesmentioning

confidence: 99%

“…Since few previous studies have assessed the effectiveness of prophylaxis by direct measurement of antibiotic levels both in plasma and tissue [18][19][20][21], we designed an experimental study to quantitatively evaluate amoxicillin concentrations in children ready for tonsillectomy and to compare these plasma and tissue levels with the Minimal Inhibitory Concentrations (MIC) of the bacteria more commonly involved in the upper airways infections.…”

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confidence: 99%

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Evaluation of amoxicillin plasma and tissue levels in pediatric patients undergoing tonsillectomy

Averono¹,

Vidali

Olina³

et al. 2010

International Journal of Pediatric Otorhinolaryngology

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Section: Discussionsupporting

confidence: 90%

Section: Subjects and Samplesmentioning

confidence: 99%

mentioning

confidence: 99%

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Evaluation of amoxicillin plasma and tissue levels in pediatric patients undergoing tonsillectomy

Averono¹,

Vidali

Olina³

et al. 2010

International Journal of Pediatric Otorhinolaryngology

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“…The administration of amoxicillin in combination with clavulanic acid does not influence the absorption of either drug (52). Furthermore, the bioavailability was not affected by food (16).…”

Section: Discussionmentioning

confidence: 99%

Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid

Deppermann

Lode

Höffken

et al. 1989

Antimicrob Agents Chemother

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Two randomized double-blind crossover studies and one randomized crossover study were performed to document possible drug-drug interactions between antacids (aluminum magnesium hydroxide, 10 ml per dose for 10 doses), antimuscarinic drugs (pirenzepine, 50 mg per dose for 4 doses), and H2-blockers (ranitidine, 150 mg per dose for 3 doses) and amoxicillin (1,000 mg), cephalexin (1,000 mg), doxycycline (200 mg), and amoxicillin-clavulanic acid (625 mg). Ten healthy volunteers participated in each study. Concentrations in serum and urine were measured by bioassay, and pharmacokinetic parameters were calculated by the usual open one-or two-compartment models (statistics were determined by the Wilcoxon test). The antacid, pirenzepine, and ranitidine had no influence on the bioavailability of amoxicillin, cephalexin, and amoxicillinclavulanic acid. Only small differences could be observed in the pharmacokinetic parameters, but they are not of therapeutic importance. However, the antacid caused a significant (P < 0.01) reduction in the gastrointestinal absorption of doxycycline (area under the concentration-time curve, 38.6 + 22.7 mg * h/liter, fasting; 6.0 + 3.2 mg. h/liter, with antacid), resulting in subtherapeutic levels of doxycycline.

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“…Agar diffusion assay of penicillins with Sarcina lutea as the test organism is preferred, as clavulanic acid does not inhibit this organism (Adam et al 1982;Schaad et al 1983;Witkowski et al 1982). Inhibition of the iJ-lactamase of a susceptible organism on penicillin-seeded medium is used as the microbiological assay for clavulanic acid and achieves a sensitivity of better than 0.2 mg/L (Adam et al 1982).…”

Section: Assay Methodsmentioning

confidence: 99%

Clinical Pharmacokinetics of Enzyme Inhibitors in Antimicrobial Chemotherapy

Watson

Stewart

Platt

1988

Clinical Pharmacokinetics

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The effectiveness of some antimicrobial agents can be enhanced by using them in combination; such combinations are termed synergistic. Where one compound potentiates the effect of a second drug they may be coformulated. Inhibition of the bacterial degradation of an active antimicrobial is the basis of clavulanate and sulbactam-potentiated penicillin combinations, and inhibition of degradative pathways in the host is the rationale behind imipenem/cilastatin therapy. Trimethoprim/sulphonamide combinations depend on the maintenance of an effective ratio for synergistic action. In order to achieve potentiation the coformulated drugs should have similar pharmacokinetics. Trimethoprim was originally matched with sulphamethoxazole, since these two drugs have similar elimination half-lives, but the significantly poorer penetration of sulphonamides, their greater non-renal clearance, the emergence of resistance, and the adverse reactions attributable to them argue against the rationale that underlies their coformulation. Time-dependent inhibition of bacterial beta-lactamases by clavulanic acid and sulbactam has extended the use of penicillins which are highly susceptible to beta-lactamase inactivation. The beta-lactamase inhibitors must penetrate to the same extent as the penicillin used with them, and be present long enough to effect inhibition; thus, rapid penetration, similar or slower elimination and equivalent volume of distribution are necessary. These requirements are met for amoxycillin/clavulanic acid, ticarcillin/clavulanic acid and ampicillin/sulbactam combinations. Clavulanic acid is absorbed orally and is given with amoxycillin. However, since sulbactam is labile by this route, the combination of sulbactam with ampicillin to form the prodrug sultamicillin has been necessary to enable an oral form to be developed. Imipenem is metabolised by renal brush-border dehydropeptidases, and may cause proximal tubular necrosis. Cilastatin was designed to inhibit this metabolism, which it effectively does, thereby both potentiating the effect of imipenem and avoiding toxicity. Appropriate matching of the kinetics of coformulated drugs is intended to maximise potentiation and minimise the risk of emergent resistance. The kinetics of the above combinations are discussed in the light of these requirements and the effects of age and disease.

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Pharmacokinetic studies of amoxicillin, potassium clavulanate and their combination

Cited by 18 publications

References 13 publications

Evaluation of amoxicillin plasma and tissue levels in pediatric patients undergoing tonsillectomy

Evaluation of amoxicillin plasma and tissue levels in pediatric patients undergoing tonsillectomy

Influence of ranitidine, pirenzepine, and aluminum magnesium hydroxide on the bioavailability of various antibiotics, including amoxicillin, cephalexin, doxycycline, and amoxicillin-clavulanic acid

Clinical Pharmacokinetics of Enzyme Inhibitors in Antimicrobial Chemotherapy

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