Kinetics of methylprednisolone and its hemisuccinate ester

Abstract

Methylprednisolone in the form of its hemisuccinate ester was injected intravenously in doses of 10 mg/kg and 63.1 mg. Plasma levels of methylprednisolone and of the ester were measured and their kinetics were calculated. Results indicate dose dependency in the kinetics of both. About 10% of the dose was excreted unchanged as hemisuccinate in the urine, indicating incomplete conversion of the prodrug. When methylprednisolone (80 mg) was also taken by mouth, the relative bioavailability of the tablets was 99%. Saliva levels of methylprednisolone were low but paralleled plasma levels in the postdistribution phase. No methylprednisolone hemisuccinate was found in saliva.

Pharmacokinetics and pharmacodynamic modeling of direct suppression effects of methylprednisolone on serum cortisol and blood histamine in human subjects

“…Animal studies indicate that esterases responsible for the hydrolysis of succinate esters are primarily present in the liver. 38 The amount of methylprednisolone succinate in urine was consistent with that previously reported for higher doses, 36 averaging 9% to 10% of the administered dose. The CL R was also independent of dose, averaging about 110 to 120 ml/hr/kg.…”

“…Mean CL values in the range of 76 to 108 L/hr were higher than previously reported by Derendorf,36 who reported mean CL values that averaged about 48 L/hr after a 63.1 mg intravenous dose.…”

Methylprednisolone pharmacokinetics after intravenous and oral administration.

“…The plasma elimination half-life and the MRT of MP remained constant with dose (Table 1) consistent with the findings of others for methylprednisolone (Szefler et al, 1986;Shah et al, 1987), prednisolone and other natural and synthetic steroids (Gustavson & Benet, 1985;Brady et al, 1987;Rohdewald et al, 1987;Al-Habet & Rogers, 1980, 1989 (Derendorf et al, 1985;Assael et al, 1982 …”

“…Figure 1 clearly demonstrates the rapid in vivo hydrolysis of MPSS followed by the generation of MP. Rapid hydrolysis of other MP ester prodrugs was reported by others (Derendorf et al, 1985;Antal et al, 1983;Shah et al, 1987). The in vitro hydrolysis of MPSS was extremely slow in all incubation fluids (Figure 2).…”

“…The pharmacokinetic characteristics of MP in relation to dose are still a subject of debate since doseindependent pharmacokinetics were reported by some (Szefler et al, 1986;Assael et al, 1982;Shah et al, 1987;Weber et al, 1988;Derendorf et al, 1988) but not by others (Derendorf et al, 1985;1987). The details of the work of Derendorf etal.…”