Misoprostol pharmacokinetics

Pharmacokinetics The pharmacokinetics following oral administration of a single dose or multiple doses of diclofenac/misoprostol to healthy subjects under fasted conditions are similar to the pharmacokinetics of the 2 individual components. Food decreases the multiple-dose bioavailability profile of both formulations. 

Pharmacokinetics Misoprostol is extensively absorbed, with a time-to-reaoh peak eoneentration of misoprostol aeid of 12 minutes and a terminal half-life of 20 to 40 minutes. Plasma steady-state was aehieved within 2 days. The serum protein binding of misoprostol aeid is less than 90%. 

Khan RU, El-Refaey H. Pharmacokinetics and adverse-effect profile of rectally administered misoprostol in the third stage of labor. Obstet Gynecol 2003 101 968-74. 

Rainsford, K.D. James, C. Hunt, R.H. Stetsko, P.I. Rischke, J.A. Karim, A. Nicholson, P.A. Smith, M. Hantsbarger, G. Effects of misoprostol on the pharmacokinetics of indomethacin in human volunteers. Clin.Pharmacol.Ther., 1992,51,415—421 [plasma ketoprofen is IS extracted indomethacin pharmacokinetics]... 

Small RE, Wilmot-Pater MG, McGee BA, Willis HE, Effects of misoprostol or ranitidine on ibuprofen pharmacokinetics. Clin Pharm (1991) 10, 870-2. 

Kendall MJ, Gibson R, Walt RP. Co-administration of misoprostol or ranitidine wifti in-domethacin effects on pharmacokinetics, abdominal symptoms and bowel habit Aliment Pharmacol Ther ( 992) 6, 437-46. 

Misoprostol increases the incidence of abdominal pain and diarrhoea when used with diclofenac or indometacin. Isolated cases of neurological adverse effects have been seen with naproxen or phenylbutazone given with misoprostol. However, no important pharmacokinetic interactions seem to occur between aspirin, diclofenac, ibuprofen or indometacin and misoprostol. NSAIDs are reported not to affect the abortive effects of intravaginal misoprostol. 

No clinically important pharmacokinetic interactions have been found to occur between aspirin 975 mg and misoprostol 200 micrograms, or between ibuprofen and misoprostol. One study found that misoprostol 800 micrograms daily decreased the AUC of a single 100-mg dose of diclofenac by a modest 20%. However, other studies have found that misoprostol had no effect on steady-state diclofenac pharmacokinetics. One study found that misoprostol 200 micrograms raised the steady-state levels of indometacin 50 mg three times daily by about 30%, whereas another found that misoprostol 400 micrograms twice daily reduced the AUC of indometacin 50 mg twice daily by 13% after one dose and reduced the maximum steady-state plasma concentration by 24%. These modest changes in serum indometacin levels are unlikely to be clinically important. 

DammannHG, Simon-Schultz J, Steinhoff I, Damaschke A, SchmoldtA, SallowskyE. Differential effects of misoprostol and ranitidine on the pharmacokinetics of diclofenac and gastrointestinal s3nnptoms. BrJ Clin Pharmacol (1993) 36, 345-9. 

Karim A. Pharmacokinetics of diclofenac and misoprostol when administered alone or as a combination product Drugs (1993) 45 (Suppl 1), 7-14. 

Lima DR, Santos RM, Wemeck E, Andrade GN. Effect of orally administered misoprostol and cimetidine on the steady state pharmacokinetics of diazepam andnordiazepam inhuman volunteers. EurJ Drug Metab Pharmacokinet ( 99 ) 16,161-70. 

Misoprostol does not significantly alter the pharmacokinetics of propranolol. 

In 12 healthy subjects misoprostol 4(X) micrograms twice daily raised the AUC of propranolol 80 mg twice daily by about 20 to 40%, and this remained raised 7 days after misoprostol was discontinued. However, as these findings were unexpected, the authors conducted a randomised, crossover, placebo-controlled study and ensured that propranolol was at steady state before assessing the effect of misoprostol. No significant effects on the pharmacokinetics of propranolol were found. No special precautions would therefore seem necessary during concurrent use. 

Bennett PN, Fenn GC, Notarianni LJ. Potential drug interactions with misoprostol effects on the pharmacokinetics ofantip3mne and propranolol. PostgradMedJ 9ZZ ) 64 (Suppl 1), 21-4. 

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