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. 1991 Apr;35(4):665–671. doi: 10.1128/aac.35.4.665

Pharmacokinetics of the penem CP-65,207 and its separate stereoisomers in humans.

G Foulds 1, A K Knirsch 1, J D Lazar 1, T G Tensfelt 1, N Gerber 1
PMCID: PMC245076  PMID: 2069372

Abstract

CP-65,207 is a new broad-spectrum penem antimicrobial agent that is a 1:1 mixture of two stereoisomers. Five minutes after a 10-min intravenous infusion of 1 g of CP-65,207 to volunteers, mean concentrations in serum were 33 micrograms of the R isomer per ml and 29 micrograms of the S isomer per ml. Following rapid distribution, half-lives of the isomers were 53 and 55 min, respectively. Concentrations in urine exceeded 800 micrograms of each isomer per ml. Recovery of the S isomer in urine (46%) was much greater than recovery of the R isomer (26%). The serum kinetics of the S isomer (volume of distribution, 319 ml/kg; total clearance, 315 ml/min; elimination rate constant, 0.80 h-1 were similar when it was given alone and when it was contained in CP-65,207, demonstrating that the presence of the R isomer has little effect on the serum kinetics of the S isomer. However, when the S isomer was given alone, the urinary recovery of intact S isomer (36%) was substantially lower than that when it was given with the R isomer as CP-65,207 (57%). Administration of the S isomer alone did not produce the unpleasant sulfurous odor in urine that was observed following administration of CP-65,207. Oral doses of a prodrug, which contained 1 g of CP-65,207, produced peak concentrations in serum of 1.6 micrograms of the R isomer per ml and 1.8 micrograms of the S isomer per ml. Approximately 36% of the S-isomer component was absorbed, and 20% of this isomer was recovered in urine. A 1-g oral dose of the prodrug of the single S isomer provides concentrations in serum above 1.0 microgram/ml (the MIC for 90% of over 1,000 hospital pathogens) for 3.5 h, suggesting that the drug given orally will prove to be efficacious against many infections.

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Selected References

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  1. Bax R. P., Bastain W., Featherstone A., Wilkinson D. M., Hutchison M., Haworth S. J. The pharmacokinetics of meropenem in volunteers. J Antimicrob Chemother. 1989 Sep;24 (Suppl A):311–320. doi: 10.1093/jac/24.suppl_a.311. [DOI] [PubMed] [Google Scholar]
  2. Chung M., Radwanski E., Loebenberg D., Lin C. C., Oden E., Symchowicz S., Gural R. P., Miller G. H. Interspecies pharmacokinetic scaling of Sch 34343. J Antimicrob Chemother. 1985 Jun;15 (Suppl 100):227–233. doi: 10.1093/jac/15.suppl_c.227. [DOI] [PubMed] [Google Scholar]
  3. Drusano G. L., Standiford H. C., Bustamante C., Forrest A., Rivera G., Leslie J., Tatem B., Delaportas D., MacGregor R. R., Schimpff S. C. Multiple-dose pharmacokinetics of imipenem-cilastatin. Antimicrob Agents Chemother. 1984 Nov;26(5):715–721. doi: 10.1128/aac.26.5.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Franceschi G., Foglio M., Alpegiani M., Battistini C., Bedeschi A., Perrone E., Zarini F., Arcamone F., Della Bruna C., Sanfilippo A. Synthesis and biological properties of sodium (5R, 6S, 8R)-6 alpha-hydroxyethyl-2-carbamoyloxymethyl-2-penem-3-carboxylate (FCE 22101) and its orally absorbed esters FCE 22553 and FCE 22891. J Antibiot (Tokyo) 1983 Jul;36(7):938–941. doi: 10.7164/antibiotics.36.938. [DOI] [PubMed] [Google Scholar]
  5. Gootz T., Girard D., Schelkley W., Tensfeldt T., Foulds G., Kellogg M., Stam J., Campbell B., Jasys J., Kelbaugh P. Pharmacokinetic studies in animals of a new parenteral penem CP-65,207 and its oral prodrug ester. J Antibiot (Tokyo) 1990 Apr;43(4):422–432. doi: 10.7164/antibiotics.43.422. [DOI] [PubMed] [Google Scholar]
  6. Gootz T., Retsema J., Girard A., Hamanaka E., Anderson M., Sokolowski S. In vitro activity of CP-65,207, a new penem antimicrobial agent, in comparison with those of other agents. Antimicrob Agents Chemother. 1989 Aug;33(8):1160–1166. doi: 10.1128/aac.33.8.1160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gural R., Lin C., Chung M., Oden E., Digiore C. Oral absorption and tolerance in man, of a new penem antibiotic, Sch 29428. J Antimicrob Chemother. 1982 Feb;9 (Suppl 100):239–243. doi: 10.1093/jac/9.suppl_c.239. [DOI] [PubMed] [Google Scholar]
  8. Guthikonda R. N., Cama L. D., Quesada M., Woods M. F., Salzmann T. N., Christensen B. G. Structure-activity relationships in the 2-arylcarbapenem series: synthesis of 1-methyl-2-arylcarbapenems. J Med Chem. 1987 May;30(5):871–880. doi: 10.1021/jm00388a022. [DOI] [PubMed] [Google Scholar]
  9. Kahan F. M., Kropp H., Sundelof J. G., Birnbaum J. Thienamycin: development of imipenen-cilastatin. J Antimicrob Chemother. 1983 Dec;12 (Suppl 500):1–35. doi: 10.1093/jac/12.suppl_d.1. [DOI] [PubMed] [Google Scholar]
  10. Kim C. U., Misco P. F., Luh B. Y., Hitchcock M. J. Synthesis and in vitro activity of C-2 quaternary heterocyclic alkylthio carbapenems. J Antibiot (Tokyo) 1987 Dec;40(12):1707–1715. doi: 10.7164/antibiotics.40.1707. [DOI] [PubMed] [Google Scholar]
  11. Loebenberg D., Miller G. H., Moss E. L., Jr, Oden E., Hare R. S., Chung M., Waitz J. A. Evaluation of the in-vitro activity of Sch 29482. J Antimicrob Chemother. 1982 Feb;9 (Suppl 100):221–231. doi: 10.1093/jac/9.suppl_c.221. [DOI] [PubMed] [Google Scholar]
  12. Norrby S. R., Björnegård B., Ferber F., Jones K. H. Pharmacokinetics of imipenem in healthy volunteers. J Antimicrob Chemother. 1983 Dec;12 (Suppl 500):109–124. doi: 10.1093/jac/12.suppl_d.109. [DOI] [PubMed] [Google Scholar]
  13. Norrby S. R., Rogers J. D., Ferber F., Jones K. H., Zacchei A. G., Weidner L. L., Demetriades J. L., Gravallese D. A., Hsieh J. Y. Disposition of radiolabeled imipenem and cilastatin in normal human volunteers. Antimicrob Agents Chemother. 1984 Nov;26(5):707–714. doi: 10.1128/aac.26.5.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Webberley J. M., Wise R., Andrews J. M., Ashby J. P., Wallbridge D. The pharmacokinetics and tissue penetration of FCE 22101 following intravenous and oral administration. J Antimicrob Chemother. 1988 Apr;21(4):445–450. doi: 10.1093/jac/21.4.445. [DOI] [PubMed] [Google Scholar]
  15. Wise R., Logan M., Cooper M., Ashby J. P., Andrews J. M. Meropenem pharmacokinetics and penetration into an inflammatory exudate. Antimicrob Agents Chemother. 1990 Aug;34(8):1515–1517. doi: 10.1128/aac.34.8.1515. [DOI] [PMC free article] [PubMed] [Google Scholar]

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