|
In
Vitro Effects of NRTIs
Drug |
Inhibition
pol g |
Inhibition
mt DNA |
%
Increase
lactic acid |
| ABC |
- |
- |
Not
done |
| 3TC |
- |
- |
Not
done |
| ZDV |
± |
± |
10 |
| d4T |
++ |
+ |
30 |
| ddI |
++ |
ND |
10 |
| ddC |
+++ |
+++
|
40 |
•
The interaction with human DNA polymerases has been studied in vitro
for all of the available NRTIs. Additional studies have been performed
related to the inhibition of mitochondrial DNA as well as the amount
of lactic acid produced.
• As can be seen here, the most inhibitory interaction with DNA
polymerase gamma has been demonstrated among the so-called d drugs,
namely d4T, ddI, and ddC.1 While interaction has been observed with
zidovudine, it is not inhibitory.
• Both d4T and ddC have also been found to inhibit mitochondrial
DNA. As yet, there are no data available for ddI.
• When increases in lactic acid production were studied, ddC
was responsible for the largest increase, 30%, followed by d4T, ddI,
and ZDV. There are no data yet available on abacavir and 3TC.
Reference:
1. Brinkman K, ter Hofstede HJM, Burger DM et al. Adverse effects
of reverse transcriptase inhibitors: mitochondrial toxicity as common
pathway. AIDS. 1998;12:1735-44.
|
|
