Reference

The pharmacokinetics of imipenem (thienamycin-formamidine) and the renal dehydropeptidase inhibitor cilastatin sodium in normal subjects and patients with renal failure

The pharmacokinetics of imipenem (thienamycin-formamidine) and the renal dehydropeptidase inhibitor cilastatin sodium in normal subjects and patients with renal failure. Verpooten, G. A.; Verbist, L.; Buntinx, A. P.; Entwistle, L. A.; Jones, K. H.; De Broe, M. E. (Dep. Nephrol., Univ. Hosp. Antwerpen, Edegem B-2520, Belg.). Br. J. Clin. Pharmacol., 18(2), 183-93 (English) 1984. CODEN: BCPHBM. ISSN: 0306-5251. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Subjects with normal renal function and patients with different degrees of renal insufficiency received i.v. 250 mg imipenem (I) [64221-86-9] alone and the cilastatin-I mixt. (II-I mixt.) [92309-29-0] (250 mg II plus 250 mg I). The mean plasma half-life of imipenem varied from 52 min in subjects with normal renal function to 173 min in subjects with end-stage renal failure studied while off-dialysis. The plasma half-life of imipenem was not affected by the co-administration of cilastatin. The mean plasma half-life of cilastatin varied from 54 min in normals to 798 min in patients with end-stage renal failure. The co-administration of cilastatin resulted in an increase of the urinary concn. and in the urinary recovery of imipenem, the effect being more pronounced in the subject with normal or only mildly impaired renal function. The plasma clearance of imipenem was decreased when cilastatin was co-administered, possibly due to inhibition of tubular secretion of imipenem. Elimination studies performed during hemodialysis indicated efficient removal of both imipenem and cilastatin during a 4 h session. In view of the important increase in half-life of cilastatin as a function of increasing renal failure, a dosage redn. is proposed in patients with severe renal failure. It is recommended that the max. dose of imipenem/cilastatin would be limited to either 1000/1000 mg twice daily or 500/500 mg four times daily in patients with a creatinine clearance of less than 15 mL/min. Also, a supplementary dose of imipenem and cilastatin after dialysis is recommended.

Pharmacokinetics of Imipenem with Cilastatin in healthy young volunteers and in elderly surgical patients

Pharmacokinetics of Imipenem with Cilastatin in healthy young volunteers and in elderly surgical patients. Wittman, D. H.; Kuipers, T.; Fock, R.; Fedder, J. (Chirur. Abt., Allg. Krankenhauses Altona, Hamburg, Fed. Rep. Ger.). Z. Antimikrob. Antineoplast. Chemother., 2(1-2), 89-97 (German) 1984. CODEN: ZAACEF. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) A crossover study was performed to investigate the blood and urine pharmacokinetics of imipenem (I) [64221-86-9] in eight healthy young volunteers after administration of a I-Cilastatin mixt. (1:1) [92309-29-0] at 500 and 1000 mg given i.v. over 15 min. Addnl., I pharmacokinetics were studied in 12 elderly surgical patients receiving a 1000-mg dose of the I-Cilastatin mixt. The I serum concns. best fit an open 2-compartment model; the parameters obtained in volunteers were (values after 500 mg in parentheses): total body clearance = 10.3 (8.4) L/h, AUC = 97 (60) mg.h/L, t1/2b = 60 (44) min, V(b) = 14.9 (8.9) L. The parameters of the patient group were: total body clearance = 6.5 L/h, AUC = 153 mg.h/L, t1/2b = 79 min and V(b) = 12.41. Significant differences in total clearance and t1/2b were found between patients and volunteers after the 1000-mg dose.