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 1.5g 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 µmol/l for 1.5g 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 µmol/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.
Highlights
Active antiretroviral therapy (HAART) is the current standard treatment for HIV infection but is associated with long term side effects
One patient was taking an antiretroviral regime consisting of a protease inhibitors (PI) and an nonnucleoside reverse transcriptase inhibitors (NNRTI) only
There was no significant difference between any of the plasma levels (ALCAR and Lcarnitine) in the treatment groups
Summary
Active antiretroviral therapy (HAART) is the current standard treatment for HIV infection but is associated with long term side effects. Nucleoside reverse transcriptase inhibitors (NRTI’s), a major component of HAART, are associated with distal symmetrical polyneuropathy (DSP) [1]. This antiretroviral toxic neuropathy (ATN) occurs mainly but not exclusively with dideoxynucleotide analogue agents, e.g. stavudine and didanosine, and causes significant morbidity in 10-35% of patients [2,3]. NRTI’s interfere with mitochondrial metabolism by reducing neuronal mitochondrial DNA synthesis leading to a disruption of oxidative metabolism [1,4,5,6]. Peripheral axons die back as the neuronal mitochondria are unable to meet their metabolic requirements. Histological examination confirms reduced epidermal innervation in affected areas [7,8]
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