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Anesthesiology. 1981 Feb;54(2):100-6.

Clinical characteristics and biotransformation of sevoflurane in healthy human volunteers.

Abstract

Sevoflurane was submitted to phase-1 studies in man following extensive testing in animal species during maintenance, was administered with oxygen to produce one hour of anesthesia in six healthy adult male volunteers. Respiratory and cardiovascular functions, the electroencephalogram, arterial blood gases, blood sevoflurane, inorganic fluoride and total, nonvolatile fluorine concentrations, and inspired and mixed expired sevoflurane concentrations were measured during exposure. Concentrations of expired sevoflurane, blood and urinary fluoride, and total nonvolatile fluorine metabolites were also measured after anesthesia. During exposure spontaneous respiratory frequency increased 28 per cent, respiratory minute volume changed insignificantly, and PaCO2s averaged 50 torr. PaCO2s remained near 400 torr. Arterial systolic blood pressure declined an average of 17 per cent. Pulse rate changed insignificantly. After an hour of exposure arterial blood serum inorganic fluoride concentrations averaged 22 microM and plasma nonvolatile organic fluorine concentrations averaged 9.1 mg/l, or 61.3 microM. Uptake of sevoflurane averaged 94 (+/- 63 SD) mmol. Following exposure 37 (/+- 12) mmol of unaltered sevoflurane were estimated to be excreted in exhaled air and 0.90 mmol of inorganic fluoride were excreted in the urine. Recoveries in exhaled air and urine averaged 51.5 (+/- 22.4) per cent of uptake. There was no significant drug-exposure-related change in the chest radiogram, electrocardiogram, electroencephalogram, urinalysis results, complete blood count, prothrombin time, serum electrolytes, transaminases, or hepatic and renal functions during four weeks following exposure compared wth preexposure values. Sevoflurane produced anesthesia of excellent quality; it appears to undergo limited biotransformation and to have little or no systemic toxicity.

PMID:
6781380
[Indexed for MEDLINE]

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