1 The potential for a drug interaction between cyclosporin A and midazolam was investigated since both compounds appear to be metabolized by the same cytochrome P-450 isoenzyme. 4 The pharmacokinetics of a single intravenous dose of midazolam (0.075 mg kg-') was studied in nine patients receiving cyclosporin A to prevent rejection of their transplanted kidneys. The average steady state blood concentrations of cyclosporin A, measured by r.i.a. using a specific monoclonal antibody, varied during a dosing interval between 175 and 600 ng ml-'.5 In these patients the hepatic elimination of midazolam was characterized by a mean t½, (± s.d.) of 2.3 ± 1.2 h and a plasma clearance (CL) of 414 ± 95 ml min-'. These values were not different from those of normal human subjects (t,, = 1.5 to 4 h, CL = 350 to 700 ml min-').6 From the results of the in vitro experiments it is concluded that cyclosporin A may potentially inhibit drug metabolism. However, therapeutic blood concentrations in vivo do not appear to be sufficient to result in an effective impairment of the hepatic elimination of midazolam when given concomitantly.
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