Methylprednisolone half-life during simultaneous barbiturate treatment and mechanical hyperventilation of neurosurgical patients.

The pharmacokinetics of methylprednisolone sodium succinate (MP) were studied in six neurosurgical patients under intensive treatment with large doses of MP, barbiturates, and mechanical hyperventilation. The study showed a remarkable level of enzyme induction within 24 hours after starting treatment, when the first blood samples were taken. The half-life (t 1/2) for MP during barbiturate and hyperventilation therapy was found to be reduced by a mean 55% (p less than 0.01) in relation to the t 1/2 of MP when administered alone. Studies on the day after termination of barbiturate intake indicated a tendency for an increase in the t 1/2 of MP, but it was not significantly different from the pretermination assessment (p greater than 0.05). On the basis of this study it is not possible to determine if the change in t 1/2 alone is governed by enzyme induction or by a combination of this plus a change in the distribution and clearance of the steroid. The clinical implication of these findings is that patients who are undergoing steroid treatment and at the same time are sedated with barbiturates should have their MP dose increased in order to compensate for the marked reduction of t 1/2 of MP.