Accession to high altitude (HA) causes environmental stress i.e. hypobaric hypoxia (HH) which may alter the hepatic
metabolism and pharmacokinetics (DMPK) of drugs. As a result the drug dose required for safe and effective therapy
may also vary at HA. The present study aims to evaluate the effect of acute hypobaric hypoxia (AHH) exposure on DMPK of
ibuprofen. Experimental rats were exposed for 6 and 24 h duration at a simulated altitude of 7620m in decompression chamber.
Ibuprofen at dose of 80 mg/kg body weight was administered orally. No statistically significant difference was observed in the
PK variables in plasma of 6 h hypoxia exposed group. However, elimination half life (T?) and mean residence time (MRT) of
ibuprofen significantly increased by 1.5 fold (p < 0.05) in 24 h hypoxia exposed group in comparison to unexposed group. A
significant reduction in GST activity by 15% at 6 h and 23% at 24 h (p < 0.05) was observed in hypoxic group. The AST levels were
significantly increased by 20-24% (p < 0.05) after AHH exposure. A significant down-regulated CYP2C9 protein level and mild
histopathological changes were also observed after 24 h AHH exposure. Thus, the results imply that AHH exposure of 24 h cause
alterations in phase II drug metabolism, CYP2C9 expression, PK and liver histology as well as liver function by ibuprofen under
AHH. This could be therapeutically relevant, however, additional investigation under chronic hypoxic conditions is required.
Shefali Gola is pursuing her Ph.D from Bharathiar University, Coimbatore in Life Sciences. She is Senior Research Fellow at Defence Institute of
Physiology and Allied Sciences (DIPAS), Defence R&D Organisation, Delhi.
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