Steady-State Pharmacokinetics of Lamivudine in Human Immunodeficiency Virus-Infected Patients with End-Stage Renal Disease Receiving Chronic Dialysis

Abstract

The steady-state pharmacokinetics of lamivudine were evaluated in 11 subjects with human immunodeficiency virus infection and end-stage renal disease, 9 of whom were receiving hemodialysis and 2 of whom were receiving chronic ambulatory peritoneal dialysis (CAPD). All subjects received 150 mg of lamivudine daily for at least 2 weeks prior to sampling for determination of the pharmacokinetics of lamivudine over a 24-h period on 2 consecutive days. On the first day, subjects received 150 mg of oral lamivudine and underwent dialysis (hemodialysis or CAPD). On the second day, subjects received another 150 mg of oral lamivudine but dialysis was not performed. For the subjects undergoing hemodialysis, the geometric mean predose serum lamivudine concentration was 1.14 g/ml (95% confidence interval [CI], 0.83 to 1.58 g/ml), the geometric mean maximum concentration in serum (C max ) was 3.77 g/ml (95% CI, 3.01 to 4.71 g/ml), and the geometric mean area under the serum concentration-time curve from time zero to 24 h (AUC 0-24 ) was 49.8 g ⅐ h/ml (95% CI 39.1 to 63.6 g ⅐ h/ml). Hemodialysis removed approximately 28 mg of lamivudine but had no significant effect on C max or AUC 0-24 . In the absence of hemodialysis, the geometric mean lamivudine terminal elimination half-life was 17.2 h (95% CI, 10.5 to 28.1 h), whereas the geometric mean intradialysis half-life of lamivudine was 5.3 h (95% CI, 3.4 to 8.2 h). The pharmacokinetics of lamivudine in subjects undergoing CAPD were similar to those in subjects undergoing hemodialysis. CAPD removed 24 mg of lamivudine over a 24-h period but had no effect on C max or AUC 0-24 . Pharmacokinetic modeling suggests that a lamivudine dose of 25 mg daily in hemodialysis subjects would provide serum exposure similar to that provided by a dose of 150 mg twice daily in patients with normal renal function.

Hepatitis B virus infection in dialysis patients

“…However, because lamivudine has a large volume of distribution, the amount of drug removed during dialysis is small compared with the total pool. Therefore, dialysis per se appears to have little impact on the overall dosing regimen, although dosing after hemodialysis is advisable 70 …”

“…Therefore, dialysis per se appears to have little impact on the overall dosing regimen, although dosing after hemodialysis is advisable. 70 In contrast, despite the recommendation on dose adjustment for renal insufficiency, it has been reported that a dosage grossly higher than the recommended renal dose can still be well tolerated in dialysis patients. In the report, hemodialysis patients with HIV infection were treated with lamivudine 150 mg daily, sixfold the recommended renal dose, and yet no obvious adverse effects were observed after several months of treatment.…”

“…In the report, hemodialysis patients with HIV infection were treated with lamivudine 150 mg daily, sixfold the recommended renal dose, and yet no obvious adverse effects were observed after several months of treatment. 70 Therefore, it appears that lamivudine is a safe drug with a high therapeutic index, even in patients with severe renal dysfunction. Although the recommended dose is 10 mg daily, based on pharmacokinetic studies for treating HBV infection in patients with end-stage renal failure with or without dialysis, the optimal effective dose of lamivudine and duration of treatment in this group of patients remain unclear.…”

Abacavir/lamivudine/dolutegravir single tablet regimen in patients with human immunodeficiency virus and end-stage renal disease on hemodialysis

“…1 However, in practice, many clinicians take advantage of 3TC's wide therapeutic index, as well as its favorable side effect profile and prescribe higher than recommended doses (up to the standard daily dose of 300 mg) in patients with renal impairment. [2][3][4][5] This allows for decreased pill burden and, consequently, regimen simplification. Clinicians may have embraced this practice in the hope of avoiding the use of 3TC oral solution, typically required to achieve the recommended dose adjustment for HD.…”

Use of Highly Active Antiretroviral Therapy in Patients with Renal Insufficiency

“…Recently, pharmacokinetic modeling in patients undergoing long-term dialysis (hemodialysis and CAPD) has suggested that the amount of lamivudine removed by dialysis is small compared with the total body pool of lamivudine. 36 Hence, in patients undergoing long-term dialysis, a lamivudine dosage of 25 mg/day (given after dialysis on the day of hemodialysis) will likely provide sufficient concentration of the drug. Lamivudine is often given as a 150-mg dose after each dialysis session for patients undergoing hemodialysis, but no data exist to support the use of this dose in end-stage renal disease.…”