Effect of intermittent hypobaric hypoxia on efficacy & clearance of drugs.

Background & objectives: People travelling to high altitude for occupational, recreational or religious purposes are mostly healthy and fit but sometimes they use drugs for common ailments like influenza, acute mountain sickness or chronic disease like diabetes. Limitation of oxygen at high altitude may compromise metabolism of drugs. Hence, we undertook this study to assess the effect of hypobaric hypoxia on some commonly used drugs in rats and rabbits. Methods: Effect of intermittent hypobaric hypoxia on phenotypic expression of anesthetic drugs pentabarbitone, thiopentone and zoxazolamine (sleeping time) was assessed in rats exposed to 282.4 mm Hg equivalent to 25000 feet in a decompression chamber. Plasma clearance of some commonly used drugs was investigated in rabbits exposed to 429 mm Hg equivalent to 15000 feet. Pharmacokinetic parameters were computed by plotting drug concentration versus time curve on semi log scale. Results: A significant delay in regaining rightening reflex was observed in rats exposed to intermittent hypobaric hypoxia in response to zoxazolamine, pentobarbitone and thiopentone sodium. Pharmacokinetics of acetyl salicylic acid, gentamicin, phenobarbitone and acetazolamide showed increase in plasma half life (t1/2), decrease in elimination rate constant (kel) and hence prolonged residence of these drugs in hypoxic animals. Interpretation & conclusions: This experimental study showed that hypoxia altered therapeutic effectiveness and clearance of several drugs, in rats and rabbits exposed to intermittent hypobaric hypoxia. s0 uch studies need to be done in human volunteers to see the effect of hypoxia on pharmacokinetics of some common drugs.

Metabolism of Valproate in Traumatic Brain Injury Patients / 대한간질학회지

PURPOSE: Traumatic brain injuries induce plasma clearance of several compounds. Phenytoin is usually used for the prevention of posttraumatic seizure, and it is known that its clearance is increased in traumatic brain injury patients. Valproate is another important antiepileptic drug for the prevention of posttraumatic seizure. We evaluated the metabolism of valproate in acute traumatic brain injury patients. METHODS: Fourteen traumatic brain injury patients were selected. They were given a loading dosage (15-20 mg/kg), and maintained with valproate. Trough serum valproate level was obtained during 7-20 days after an acute injury. RESULTS: The total clearance level of valproate was higher in acute traumatic brain injury patients than patients with chronic valproate use (7.70+/-1.36 ml/kg/hr vs. 9.05+/-1.91 ml/kg/hr, p<0.05). CONCLUSIONS: Acute traumatic brain injury results in the induction of valproate metabolism during 7-20 acute days, and it is related to the enhancement of multiple metabolic pathways.