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| |  High Altitude May Affect Drug Efficacy SAN FRANCISCO, CA -- Nov. 4, 1998 -- Those who enjoy travelling 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 Demerol®, Lithium® and even widely-used high altitude sickness medications like acetazolamide. The study, performed by researchers at the University of Cincinnati and the University of Chile, will be presented at the American Association of Pharmaceutical Scientists annual meeting. The researchers said that 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, the researchers found significant changes in the drug’s pharmacokinetics. In this study they investigated if similar changes occur with acetazolamide which is recommended for the prophylaxis of acute mountain sickness. Acetazolamide, 250 mg, was administered perorally to three 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 hours and urine was collected up to 36 hours. Pharmacokinetic parameters derived from curve-fitting of plasma concentrations were analysed by ANOVA for statistical significance. It was seen that significant changes in the pharmacokinetics occurred within 24 hours. 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 percent from L to HA and increased 37 percent 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. The authors write that 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 their studies, the authors suggest 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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