Mefloquine methanesulfonate (WR-142, 490·CH3SO3H), a highly effective antimalarial agent, when infused at a dose rate of 1 mg/kg/ min for 20 min in the anesthetized dog, caused either little or no effect on the pulmonary and cardiovascular parameters measured during this drug infusion or in the following 3-hr observation period. However, dose rates of 2 and 3 mg/kg/min of mefloquine MS for 20 min did produce pulmonary and cardiovascular changes. The respiratory parameters which were observed to change were: (1) tidal volume, which fell during the drug infusion but then returned to control values during the remaining portion of the observation period; (2) respiratory rate, which rose during the drug infusion, but returned to control values; (3) dynamic airways resistance, which decreased during drug administration, but then rose above control values; (4) small gradual changes in blood pO2 and pCO2. The cardiovascular parameters observed to change were: (1) arterial blood pressure, which decreased during the drug infusion, but returned rapidly to control values; (2) cardiac contractile force, which diminished during the drug infusion and returned toward control values later in the observation period; (3) central venous pressure, which rose transiently during drug administration; (4) pulmonary artery pressure, which rose initially, but tended to decrease late in the observation period and returned to control values within a 24-hr period. The magnitude of the effects of mefloquine MS appeared to be more dependent on the dose rate of drug delivery than on the total dose delivered.
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