Effect of Zidovudine and its interaction with rocuronium on neuromuscular transmission

Abstract

Neuromuscular weakness is often found in patients receiving zidovudine therapy due to mitochondrial damage. Effect of zidovudine was evaluated in indirectly and directly stimulated isolated rat phrenic nerve hemidiaphragm preparations, by cumulative dose response curve with square wave pulses, 0.5 ms duration of 2 Hz at every 10 s. To understand the observed effect of zidovudine, interaction studies were carried out with rocuronium. Dose response curve of rocuronium was compared in the absence and in the presence of 1.2 and 12 mmol/ml zidovudine. In another set of experiment, intact animals were treated with zidovudine 50 and 100 mg/kg for 15 days and phrenic nerve hemidiaphragm was obtained for in vitro experiment. Effect of zidovudine (30 mmol/ml) on twitch responses inhibited by dantrolene 50 μmol/ml, magnesium chloride 8 mmol/ml, rocuronium 10 μmol/ml, succinylcholine 25 μmol/ml and lignocaine 600 μmol/ml was studied. Zidovudine (3-30 mmol/ml) significantly augmented the twitch responses up to 80 and 40% in indirectly and directly stimulated preparations, respectively (P<0.05). Zidovudine did not show significant interaction with rocuronium in any group as per dose response curve and inhibitory concentration 5%, inhibitory concentration 50% and inhibitory concentration 95% of rocuronium. Zidovudine (30 mmol/ml) augmented the twitch responses inhibited by dantrolene, magnesium chloride and rocuronium. It reduced the time for complete block of succinylcholine (P<0.05). Zidovudine affects the neuromuscular transmission. No conclusive interaction between rocuronium and zidovudine was found.

Keywords: Drug interaction; neuromuscular transmission; rocuronium; zidovudine.

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Effect of zidovudine on the resonses of dantrolene, magnesium chloride and rocuronium on diaphragm preparation. Grey colored bars represent (a) dantrolene (50 μ mol/ml), (b) magnesium chloride (8 mmol/ml) and (c) rocuronium (10 μ mol/ml). Dark bars represent in the presence of 30 mmol/ml zidovudine. Data expressed as mean± standard error of mean and *represents significance at P> 0.05.