Abstract
The use of nucleoside reverse transcriptase inhibitors in the treatment of HIV infection is associated with antiretroviral toxic polyneuropathy (ATN). Previous studies suggest that long term treatment with Acetyl-L-carnitine (ALCAR) 1.5 gram twice daily improves symptoms and promotes nerve regeneration. It is unknown whether the drug's pharmacokinetic profile would allow for a once daily administration. Twenty three HIV-1 infected subjects taking ALCAR for ATN were enrolled in a cross over trial and switched from twice to once daily dosing. Their regimen was changed from 1.5 g twice daily to 1g (4 patients), 2g (7), and 3g (12) once daily, respectively. Twelve healthy volunteers served as control. Plasma levels of ALCAR and its metabolite L-carnitine were measured. Patients receiving ALCAR had higher pre-dose levels than control subjects. Post dose levels were not significantly higher than pre dose levels in any treatment group. The pre / post dose ALCAR concentrations were 7.6 / 7.7, 7.1 / 6.8, 7.7 / 6.8, and 7.1 / 7.5 micromol/l for 1.5 g twice daily, 1g once daily, 2g once daily, and 3g once daily, respectively. All values were significantly higher than the mean concentration in the control group (4.3 micromol/l). For ALCAR and L-carnitine, measurements for once daily regimens did not differ from the twice daily regimen. Once daily dosing of ALCAR can achieve similar plasma levels as twice daily dosing but intra-mitochondrial levels remain unknown. The pharmacokinetic profile of orally administered ALCAR is complex and likely to be highly affected by endogenous concentrations.