Much lower dose of lamivudine needed for HIV-positive patients on dialysis
For HIV-positive patients with end-stage renal disease receiving chronic dialysis, lamivudine at 25mg once daily provides drug exposure equivalent to 150mg twice daily in similar patients with normal renal function, researchers report.
Dr Charles B Hicks and colleagues from Duke University Medical Center, Durham, North Carolina, evaluated the steady-state pharmacokinetics of lamivudine in 11 HIV-positive patients with end-stage renal disease. Nine of the patients were receiving haemodialysis and the other two were receiving continuous ambulatory peritoneal dialysis.
For at least two weeks before sampling, all patients received 150mg of lamivudine daily as part of their antiretroviral regimen, according to the report in the August issue of Antimicrobial Agents and Chemotherapy. Pharmacokinetic parameters were measured on consecutive days, with dialysis performed on one day and withheld on the second.
Dr Hicks’s team found that dialysis removed about 28mg of lamivudine without having any significant effect on mean maximum concentration in serum or in the mean area under the serum concentration-time curve from 0 to 24 hours. They attribute this to redistribution of lamivudine from the intracellular compartment.
Without dialysis the geometric mean lamivudine terminal half-life was 17.2 hours compared with 5.3 hours with dialysis, they add.
The effects of CAPD were similar to those of hemodialysis.
“In clinical practice, a dose of 150mg of lamivudine given orally once daily is well tolerated and has commonly been used for patients with end-stage renal disease undergoing haemodialysis. The data from this study suggests, however, that this dose is considerably higher than the dose needed,” Dr Hicks’s group notes.
They base this on an area-under-the-curve value of 49.8 µg x h/mL seen in their subjects, compared with typical values of about 4.5-6.6 µg x h/mL in HIV patients with normal kidneys receiving 150mg lamivudine twice daily.
“Pharmacokinetic modelling of data for the subject with the lowest area under the curve in our haemodialysis cohort indicated that administration of a dose of 25mg once daily would yield an area under the curve over the dosing interval approximating that for subjects with normal renal function receiving 150mg twice daily,” they write.
Dr Hicks and colleagues say that these data should help clinicians treat the increasing number of HIV-infected patients with end-stage renal disease safely and effectively.
Bohjanen PR, Johnson MD, Szczech LA et al. Steady-state pharmacokinetics of Lamivudine in human immunodeficiency virus-infected patients with end-stage renal disease receiving chronic dialysis. Antimicrob Agents Chemother 2002 Aug;46(8):2387-92
Source: Reuters Health