[Effects of cilastatin sodium, an inhibitor of dehydropeptidase-I, on human urinary peptide excretion. Patients with renal insufficiency].
Effects of imipenem/cilastatin sodium (IPM/CS), a new parenteral carbapenem combination antibiotic, on the excretion of urinary peptides were investigated by amino acid analysis of these peptides from 12 patients with varying degrees of impairment of renal function, after single or multiple doses (9 doses) of 500 mg/500 mg of the combination drug administered by 30-minute drip infusion. In a single dose study, slight increase in glycine (Gly) were observed in patients with mildly impaired renal function (group I). On the other hand, several amino acids including aspartic acid (Asp), glutamic acid (Glu), Gly and alanine (Ala) were increased in patients with moderately (group II) and severely (group III) impaired renal function. Gly showed the greatest increase, 1.029 microM/mg creatinine.2 hours, and the value was 2.4 times as high as the control collected before drug administration. These values were reduced to the control levels within 10-12 hours after the drug administration for amino acids showing small increases and within 12-24 hours after drug administration even for those showing greater increases. In a multiple-dose study employing 3 patients with moderately impaired renal function, Asp and Gly were found to increase after the 1st, 5th and 9th doses. The increased amino acids were reduced to preadministration levels within 10-12 hours or faster, and no tendency for accumulation was observed. From the above results, CS, as a dehydropeptidase-I inhibitor apparently caused increases in some peptides consisting mainly of Asp, Glu, Gly and Ala in patients with impaired renal function. A careful selection of dose levels and frequency of administration will be required in patients with moderately or severely impaired renal function.
D000368:Aged; D000596:Amino Acids / Q000652:urine; D015377:Cilastatin; D003521:Cyclopropanes / Q000008:administration & dosage*; D004150:Dipeptidases / Q000037:antagonists & inhibitors*; D004338:Drug Combinations; D006801:Humans; D015378:Imipenem; D007674:Kidney Diseases / Q000652:urine*; D008875:Middle Aged; D010455:Peptides / Q000652:urine*; D013845:Thienamycins / Q000008:administration & dosage*
D000596:Amino Acids; D003521:Cyclopropanes; D004338:Drug Combinations; D010455:Peptides; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D004150:Dipeptidases; C038937:dipeptidase