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 (approximately 100 1), 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.
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 (approximately 100 1), 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.
Authors: J M Pluda; T P Cooley; J S Montaner; L E Shay; N E Reinhalter; S N Warthan; J Ruedy; H M Hirst; C A Vicary; J B Quinn Journal: J Infect Dis Date: 1995-06 Impact factor: 5.226
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