Contact: Alisa Cahan 305-672-4422, [email protected]
Impact of High Altitude on Drug Efficacy
Those who enjoy traveling to exotic locations, beware. The latest research shows that staying at high altitudes for more than 24 hours can alter the effect of drugs like Demerolâ„¢, Lithiumâ„¢ and even widely-used high altitude sickness medications like acetazolamide. How can skiers, hikers and tourists determine if their medication is ineffective at high altitudes? Pharmaceutical scientists are just beginning to study the topic and have some interesting research findings.
See Abstract below:
Session: Clinical Pharmacokinetic/Pharmacodynamic Studies
Poster Session
EFFECT OF SHORT- AND LONG-TERM EXPOSURE TO HIGH ALTITUDE ON THE PHARMACOKINETICS OF ACETAZOLAMIDE.
M.A. Agrawal*1,3 , A. Arancibia2, C. Paulos2, and W.A. Ritschel1. 1University of Cincinnati, 3223 Eden Ave., M.L. 4, Cincinnati, OH 45267-0004; 2University of Chile, Santiago, Chile; 3present address: BFGoodrich, 9921 Brecksville Rd., Brecksville, OH 44141.
Purpose.
To investigate the effect of short- and long-term exposure to high altitude on the pharmacokinetics of acetazolamide. Exposure to high altitude results in significant physiologic changes and may precipitate acute mountain sickness, ranging from mild symptoms above 2,500 m to severe symptoms above 4,000 m. In a previous study with meperidine, we found significant changes in its pharmacokinetics. In this study we investigated if similar changes occur with acetazolamide which is recommended for the prophylaxis of acute mountain sickness.
Methods.
Acetazolamide, 250 mg, was administered perorally to 3 groups of 12, healthy, young, male subjects each: those residing at sea level (group L), these same subjects on day following arrival at high altitude (4,360 m, group HA), and those residing at high altitude (group HC). Serial blood samples were collected for 24 h and urine was collected up to 36 h. Pharmacokinetic parameters derived from curve-fitting of plasma concentrations were analyzed by ANOVA for statistical significance.
Results.
It was seen that significant changes in the pharmacokinetics occurred within 24 h. Some of these changes appeared to last for at least 10 months while some tended to return to values at sea level. A significant increase in the elimination rate constant (l z) from L to HA and significant increase in the total clearance uncorrected for bioavailability (CL/F) from L to HA to HC was seen. The apparent volume of distribution (Vz) decreased 17 % from L to HA and increased 37 % from HA to HC. The mean residence time (MRT) decreased significantly for HA compared to L and HC. Significant changes in the extent of protein binding, erythrocyte uptake and free acetazolamide concentrations were also seen. In contrast, the change in the amount of acetazolamide excreted in urine was not significant. Also, the fraction eliminated unchanged (Fel) in urine did not change significantly.
Conclusions.
Pharmacokinetics of drugs are usually studied at low altitude and the same values are extrapolated to patients at high altitude, due to lack of sufficient data. Based on our studies, it is suggested that tourists or residents at high altitude should be monitored for possible changes in the pharmacokinetics of drugs administered. These changes may have significant ramifications on the clinical effectiveness of a dosage regimen, which may have to be adjusted.
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