SINGLE-DOSE PHARMACOKINETICS OF LAMIVUDINE IN SUBJECTS WITH IMPAIRED RENAL-FUNCTION AND THE EFFECT OF HEMODIALYSIS

Aims The purpose of this study was to investigate the pharmacokinetics of a single oral dose of lamivudine administered to subjects with ren al impairment and to determine whether lamivudine was dialysable in su bjects with severe renal impairment undergoing haemodialysis. Methods Twenty-nine subjects were enrolled, nine with normal renal function (c reatinine clearance (CLCR) 82-117 ml min(-1)), eight with moderately i mpaired renal function (CLCR 25-49 ml min(-1)), six with severe impair ment (CLCR 13-19 ml min(-1)) and six with severe impairment who were a lso receiving haemodialysis. After an overnight fast, nondialysis subj ects received a single oral dose of lamivudine. Subjects on haemodialy sis were given two doses on separate occasions (intra and interdialysi s). Blood was obtained before lamivudine administration and at regular intervals to 48 h post dose. Timed urine collections were performed f or subjects able to produce urine. Pharmacokinetic parameters were cal culated by using standard non compartmental techniques. Results Decrea sing renal function was associated with reduced lamivudine clearance i n a proportional and apparently linear relationship. Lamivudine was we ll dialysed with an extraction ratio in the order of 50%. However, bec ause lamivudine has a large volume of distribution (approximate to 100 1), a haemodialysis session of 4 h did not affect overall exposure to a clinically significant degree in most subjects. Conclusions Impaire d renal function does require lamivudine dose modification according t o the degree of impairment, but no further modification of dose is req uired for subjects undergoing regular haemodialysis.