Single dose pharmacokinetics of lamivudine in subjects with impaired renal function and the effect of haemodialysis

ABSTRACT

Aims The purpose of this study was to investigate the pharmacokinetics of a single oral dose of lamivudine administered to subjects with renal impairment and to determine whether lamivudine was dialysable in subjects with severe renal impairment undergoing haemodialysis.

Methods Twenty-nine subjects were enrolled, nine with normal renal function (creatinine clearance (CL_CR ) 82–117  ml  min⁻¹ ), eight with moderately impaired renal function (CL_CR 25–49  ml  min⁻¹ ), six with severe impairment (CL_CR 13–19  ml  min⁻¹ ) and six with severe impairment who were also receiving haemodialysis. After an overnight fast, nondialysis subjects received a single oral dose of lamivudine. Subjects on haemodialysis were given two doses on separate occasions (intra and interdialysis). Blood was obtained before lamivudine administration and at regular intervals to 48  h post dose. Timed urine collections were performed for subjects able to produce urine. Pharmacokinetic parameters were calculated by using standard non compartmental techniques.

Results Decreasing renal function was associated with reduced lamivudine clearance in a proportional and apparently linear relationship. Lamivudine was well dialysed with an extraction ratio in the order of 50%. However, because lamivudine has a large volume of distribution (≈100  l), a haemodialysis session of 4  h did not affect overall exposure to a clinically significant degree in most subjects.

Conclusions Impaired renal function does require lamivudine dose modification according to the degree of impairment, but no further modification of dose is required for subjects undergoing regular haemodialysis.