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Acyclovir taxes Aldehyde Dehydrogenase

Gondwanaland

Senior Member
Messages
5,092
https://www.ncbi.nlm.nih.gov/pubmed/25292432
Acyclovir
Acyclovir is primarily eliminated by renal excretion. However, approximately 8.5–14.1% of the drug is metabolized by ADH to acyclovir aldehyde, which in turn is metabolized through ALDH to 9-carboxymethoxymethylguanine (CMMG) (96, 97). With impaired renal function, acyclovir renal elimination is limited, and the drug is primarily metabolized. When 1,000 mg of the acyclovir prodrug valaciclovir was given orally in Japanese patients with
end-stage renal disease, the acyclovir half-life was significantly altered by the ALDH2 genotype; patients with an ALDH2*2/*2 genotype had a prolonged half-life 8.6 h longer on average than those with an ALDH2*1/*1 genotype (26.7 h versus 18.1 h). These data suggest that metabolism of acyclovir and valaciclovir is mediated by ALDH2 (98).
@Wonkmonk
@Learner1 Would taking NAD+ and Molybdenum help?
 

Wonkmonk

Senior Member
Messages
1,006
Location
Germany
@Gondwanaland the easiest way to improve Acyclovir half-life would be co-administration with probenecid and/or cimetidine. I think a prolongation of over 50% is possible with those drugs in combination.

I also don't see the need to have additional prolongation because if you think higher serum levels are going to make a difference, you can simply take more Valacyclovir or the same dose more frequently because of its low toxicity.

Experience seems to suggest, though, that higher doses often don't produce better results and that there is an optimum somewhere between 2000mg and 6000mg a day, depending on the individual patient.
 

Gondwanaland

Senior Member
Messages
5,092
@Wonkmonk my point it to reduce its toxiciy via supplementation with NAD+ and Moly. I am not sure about reducing kidney toxicity because B3 and Moly increase purines/uric acid, so a Xanthine Oxidase inhibitor should be used as well (?)
 

Wonkmonk

Senior Member
Messages
1,006
Location
Germany
@Gondwanaland Kidney toxicity is mainly due to formation of renal calculi and can be avoided by adequate fluid intake. Dr Lerner recommends six 8-ounce glasses of water a day for his recommended 4 gram dose, which is already pretty high.

Apart from renal calculi, there is little concern about toxicity for Valacyclovir. So this is not something I'd worry much about.