Clavulanic acid pharmacokinetics

Jacobs RF, Trang JM, Kearns GL, et al. Ticarcillin/clavulanic acid pharmacokinetics in children and young adults with cystic fibrosis. J Pediatr 1985 106 1001-1007. 

As resistance to 3-lactam antibiotics increased because of the expression of a variety of 3-lactamases, many groups focused their efforts on discovering compounds that could be more reactive to 3-lactamases without having significant intrinsic antibiotic activities of their own and pharmacokinetic properties that would be similar to 3-lactam antibiotics. This focus led to the discoveries of clavulanic acid (18) and monobactam sulfazecins (19). Nature effectively stabilized the latter monobactam structure by the addition of a A-sulfamic acid. The 3-lactamase inhibitor clavulanic acid was combined with amoxicillin, which... 

The in vivo activity of a combination of clavulanic acid and amoxycillin is shown in Table 6.4 [30]. This -lactamase inhibitory activity, together with useful pharmacokinetic properties, has resulted in the development of Augmentin (potassium clavulanate in combination with amoxycillin) for oral and parenteral use and Timentin (potassium clavulanate plus ticarcillin) for parenteral use, against a wide range of bacterial infections. ... 

For commercial success, any 8-lactamase inhibitor must have the right balance of in vivo activity, stability, pharmacokinetic profile, tolerance, safety and cost-efficiency, as well as demonstrating in vitro activity against isolated enzymes and intact bacteria. To date, only clavulanic acid and sulbactam have fulfilled these stringent criteria. 

Todd PA, Benfield P. AmoxicUlin/clavulanic acid. An update of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1990 39(2) 264-307. 

Tazobactam, USP. Tazobactam is a penicillanic acid sulfone that is similar in structure to sulbactam. It is a nioK potent /3-lactamase inhibitor than sulbactam and ha.- 3 slightly broader spectrum of activity than clavulanic acid. Ii has very weak antibacterial activity. Tazobactam is available in fixed-dose, injectable combinations with piperacillin, a broad-spectrum penicillin consisting of an 8 I ratio of pipci- acillin sodium to tazobactam sodium by weight and ma-keted under the trade name Zosyn. The pharmacokineticsprotein bound, experience ven little metabolism, and are excreted in active forms in the urine in high concentrations. 

Garg, R.C., Keefe, T.J. Vig., M.M. (1987) Serum levels and pharmacokinetics of ticarcillin and clavulanic acid in dog following parenteral administration of Time-ntin . Journal of Veterinary Pharmacology and Therapeutics, 10, 324-330. 

Bawdon, R.E. Leveno, K.L. Cunningham, F.G. Nobles, B. Nelson, S. Intrapartum pharmacokinetics of ticarcillin and clavulanic acid in serum as determined by high-pressure liquid chromatography. Adv.Therapy, 1984, 1, 419-426 [derivatization SPE serum pharmacokinetics]... 

The pharmacokinetics of amoxicillin 1 g, and both amoxicillin and clavulanic acid (given as co-amoxiclav 625 mg), were not significantly altered by 10 doses of aluminium/magnesium hydroxide (Maalox) 10 mL, with the last dose given 30 minutes before amoxicillin. Another study found that four 40-mg doses of aluminium hydroxide (Aludrox) given at 20 minute intervals had no effect on the pharmacokinetics of either amoxicillin or clavulanic acid (given as co-amoxiclav 750 mg with the second dose of antacid). ... 

I. Amoxicillin and co-amoxidav. Food eaten immediately before amoxicillin reduced its serum levels by about 50% and reduced urinary excretion, when compared with the fasted state. However, in another study, a standard breakfast had no effect on the AUC of a single 500-mg dose of amoxicillin in 16 healthy subjects. Similarly, a crossover study in 18 healthy subjects given co-amoxiclav (amoxicillin 500 mg with clavulanic acid 250 mg), either 2 hours before or with a fried breakfast, found that the breakfast had no significant effect on the pharmacokinetics of amoxicillin or clavulanic acid. Moreover, a further study in 43 healthy subjects found that taking co-amoxiclav with food tended to minimise the incidence (but... 

Cimetidine 200 mg, given three times daily the day before and with a single 200-mg dose of co-amoxiclav (amoxicillin with clavulanic acid), had no significant effect on the bioavailability of amoxicillin or clavulanic acid. Another study found that ranitidine (300 mg given the day before and 150 mg given with the antibacterial) had no effect on the pharmacokinetics of a single 1-g dose of amoxicillin. ... 

No interaction normalfy occurs between digoxin and amoxicillin, cefazolin, cefuroxime, flucloxacillin, phenoxymethylpenicillin or ticarcillin/clavulanic acid. No pharmacokinetic interaction occurs between ampicillin and digitoxin. In contrast, one early study found that cefradine increased serum levels of digoxin. 

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