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Pharmacokinetics and biochemical efficacy of pirmagrel, a thromboxane synthase inhibitor, in renal allograft recipients
Author(s) -
Chouinard Michael L,
Martin Louis L,
Coffman Thomas,
Hamilton Brenda H,
Linberg Leonid F,
Pamidi Anjula,
Simke John P,
Rakhit Ashok
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.197
Subject(s) - thromboxane b2 , thromboxane a synthase , pharmacokinetics , thromboxane , urine , volume of distribution , endocrinology , nephrotoxicity , medicine , chemistry , thromboxane a2 , kidney , urinary system , excretion , pharmacology , platelet
The effects of a 48‐hour 0.5 mg/kg/hr infusion of the thromboxane synthase inhibitor pirmagrel were studied in 10 renal allograft recipients with cyclosporine nephrotoxicity. Plasma concentrations reached a mean steady‐state plasma level of 1798 ±481 ng/ml. Biphasic, rapid elimination of pirmagrel was observed with a distribution half‐life of 6.7 minutes and a terminal half‐life of 73 minutes. Plasma clearance and the volume of distribution of the drug were 300 ± 87 ml/hr/kg and 497 ± 232 ml/kg, respectively. The pharmacodynamic effects of pirmagrel were marked by a mean 96% suppression of serum thromboxane B 2 (TXB 2 ), which coincided with a suppression of urinary excretion of TXB 2 , 2,3‐dinor‐TXB 2 , and 11‐dehydro‐TXB 2 of 85% ± 8%, 91% ± 5%, and 89% ± 9%, respectively. Urinary excretion of all thromboxane metabolites measured at the end of 1 week after termination of infusion was returned to the baseline. In conclusion, pirmagrel caused effective and sustained suppression of all thromboxane derived metaboHtes in plasma and urine during continuous infusion in kidney transplant patients receiving cyclosporine. Clinical Pharmacology and Therapeutics (1992) 52 , 597–604; doi: 10.1038/clpt.1992.197