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Entry‐into‐human study with the novel immunosuppressant SDZ RAD in stable renal transplant recipients
Author(s) -
Neumayer,
Valérie Paradis,
Korn,
; Jean,
Fritsche,
Klemens Budde,
Winkler,
Kliem,
Pichlmayr,
Markus Hauser,
Burkhardt,
Lison,
Barndt,
AppelDingemanse
Publication year - 1999
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.1999.00085.x
Subject(s) - pharmacokinetics , placebo , tolerability , pharmacology , adverse effect , medicine , oral administration , alternative medicine , pathology
Aims To evaluate the tolerability of single oral SDZ RAD doses in stable renal transplant recipients and the pharmacokinetics of ascending SDZ RAD doses when coadministered with steady‐state cyclosporin A microemulsion (Neoral).Methods This randomized, double‐blind, placebo‐controlled, sequential study involved 54 patients in six treatment groups; a different SDZ RAD dose (0.25, 0.75, 2.5, 7.5, 15, 25 mg) was assessed in each group. Patients received a single oral dose of SDZ RAD (n=6) or placebo (n =3) with their usual Neoral dose. SDZ RAD and cyclosporin A pharmacokinetic parameters were determined.Results All SDZ RAD doses were well tolerated, with no discontinuations due to adverse events, serious adverse events, or deaths. Similar proportions of patients receiving SDZ RAD and placebo had at least one adverse event (44% and 50%, respectively). Mean changes in laboratory variables (baseline to endpoint) showed no clinically meaningful differences between SDZ RAD and placebo groups. SDZ RAD was absorbed rapidly and showed dose‐proportional pharmacokinetics (dose: 2.5–25 mg), based on systemic exposure. Multiple postabsorptive phases in the pharmacokinetic profile indicate tissue distribution. The elimination half‐life ranged from 24 to 35 h across the five highest dose groups. Pharmacokinetics were similar in men and women. Co‐administration of escalating single oral SDZ RAD doses did not affect steady‐state cyclosporin A pharmacokinetics.Conclusions SDZ RAD was well tolerated; safety profiles of SDZ RAD and placebo were similar. SDZ RAD pharmacokinetics were dose‐proportional across the range 2.5–25 mg in conjunction with cyclosporin A‐based therapy, according to systemic exposure. Cyclosporin A pharmacokinetics were not affected by coadministration of single oral doses of 0.25–25 mg SDZ RAD.