Abstract
The apparent diffusion coefficient of a bound drug, cefoperazone, was studied. The protein binding of cefoperazone was studied by voltammetry, a technique which permitted instant measurements. The apparent diffusion coefficients were similar in agar and fibrin and lower in rat brain tissue. The influence of protein on the value of the apparent diffusion coefficient was negligible. The hypothesis that only the free drug diffuses was supported. The percentage of binding determined by voltammetry corresponded to the true concentration of drug which diffuses and is much lower than the percentage of binding determined by the ultrafiltration centrifugation method. This discrepancy could be explained by the rate of dissociation of the protein-drug complex.
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- Allaz A. F., Dayer P., Fabre J., Rudhardt M., Balant L. Pharmacocinétique d'une nouvelle céphalosporine, la céfopérazone. Schweiz Med Wochenschr. 1979 Dec 29;109(50):1999–2005. [PubMed] [Google Scholar]
- Barza M., Cuchural G. General principles of antibiotic tissue penetration. J Antimicrob Chemother. 1985 Jan;15 (Suppl A):59–75. doi: 10.1093/jac/15.suppl_a.59. [DOI] [PubMed] [Google Scholar]
- Bergan T. Pharmacokinetics of tissue penetration of antibiotics. Rev Infect Dis. 1981 Jan-Feb;3(1):45–66. doi: 10.1093/clinids/3.1.45. [DOI] [PubMed] [Google Scholar]
- Bergeron M. G. Tissue penetration of antibiotics. Clin Biochem. 1986 Apr;19(2):90–100. doi: 10.1016/s0009-9120(86)80054-6. [DOI] [PubMed] [Google Scholar]
- Craig W. A., Welling P. G. Protein binding of antimicrobials: clinical pharmacokinetic and therapeutic implications. Clin Pharmacokinet. 1977 Jul-Aug;2(4):252–268. doi: 10.2165/00003088-197702040-00002. [DOI] [PubMed] [Google Scholar]
- Hamilton R. A., Kowalsky S. F., McCormick E. M., Echols R. M. Protein binding of ceftriaxone, cefoperazone, and ceftizoxime. Clin Pharm. 1987 Jul;6(7):567–569. [PubMed] [Google Scholar]
- Lang S. D., Cameron G. L., Mullins P. R. Anomalous effect of serum on the antimicrobial activity of cefoperazone. Drugs. 1981;22 (Suppl 1):52–59. doi: 10.2165/00003495-198100221-00012. [DOI] [PubMed] [Google Scholar]
- Meulemans A., Henzel D., Brun-Pacaud M., Mohler J., Vicart P., Huy P. T. On-line pharmacokinetics of chloramphenicol in rat cortex by in vivo electrochemical detection. Chemotherapy. 1984;30(6):353–357. doi: 10.1159/000238293. [DOI] [PubMed] [Google Scholar]
- Meulemans A., Paycha F., Hannoun P., Vulpillat M. Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues. Antimicrob Agents Chemother. 1989 Aug;33(8):1286–1290. doi: 10.1128/aac.33.8.1286. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Meulemans A., Vicart P., Henzel D., Mohler J., Vulpillat M. Cefsulodin penetration into rat brain: extracellular versus total concentration. Chemotherapy. 1986;32(5):393–398. doi: 10.1159/000238441. [DOI] [PubMed] [Google Scholar]
- Ohshima T., Johno I., Kitazawa S. Comparative evaluation of microultrafiltration devices for determination of protein binding. Ther Drug Monit. 1988;10(3):310–315. doi: 10.1097/00007691-198803000-00013. [DOI] [PubMed] [Google Scholar]
- Peterson L. R., Moody J. A., Fasching C. E., Gerding D. N. Influence of protein binding on therapeutic efficacy of cefoperazone. Antimicrob Agents Chemother. 1989 Apr;33(4):566–568. doi: 10.1128/aac.33.4.566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ryrfeldt A., Bodin N. O., Hansson E. Biliary excretion of ampicillin, azidocillin and benzylpenicillin in the rat. Acta Pharmacol Toxicol (Copenh) 1973;33(3):219–228. doi: 10.1111/j.1600-0773.1973.tb02009.x. [DOI] [PubMed] [Google Scholar]
- SCHANTZ E. J., LAUFFER M. A. Diffusion measurements in agar gel. Biochemistry. 1962 Jul;1:658–663. doi: 10.1021/bi00910a019. [DOI] [PubMed] [Google Scholar]
- Spector R., Korkin D. T., Lorenzo A. V. A rapid method for the determination of salicylate binding by the use of ultrafilters. J Pharm Pharmacol. 1972 Oct;24(10):786–789. doi: 10.1111/j.2042-7158.1972.tb08883.x. [DOI] [PubMed] [Google Scholar]
- Tillement J. P., Urien S., Chaumet-Riffaud P., Riant P., Bree F., Morin D., Albengres E., Barre J. Blood binding and tissue uptake of drugs. Recent advances and perspectives. Fundam Clin Pharmacol. 1988;2(3):223–238. doi: 10.1111/j.1472-8206.1988.tb00634.x. [DOI] [PubMed] [Google Scholar]
- Watanabe Y., Hayashi T., Takada R., Yasuda T., Saikawa I., Shimizu K. Studies on protein binding of antibiotics. I. Effect of cefazolin on protein binding and pharmacokinetics of cefoperazone. J Antibiot (Tokyo) 1980 Jun;33(6):625–635. doi: 10.7164/antibiotics.33.625. [DOI] [PubMed] [Google Scholar]