Prednisolone disposition in obese men

Milsap, Rebecca L.; Plaisance, Karen I.; Jusko, William J.

doi:10.1038/clpt.1984.263

Cited by 50 publications

(23 citation statements)

References 8 publications

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“…Further evidence suggests that adipose tissue may play a role in the increased clearance of prednisolone in obese men. 59 The interconversion of prednisolone and prednisone is dependent on 11-hydroxysteroid dehydrogenase, an enzyme present in adipose tissue; therefore, the increase in adipose tissue may provide an alternative site of clearance for prednisolone.…”

Section: Changes In Metabolic Enzymes In Obese Humanssmentioning

confidence: 99%

Pharmacokinetic Considerations in Obesity

Blouin

Warren

1999

Journal of Pharmaceutical Sciences

184

134

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Section: Changes In Metabolic Enzymes In Obese Humanssmentioning

confidence: 99%

Pharmacokinetic Considerations in Obesity

Blouin

Warren

1999

Journal of Pharmaceutical Sciences

184

134

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“…While prednisolone clearance is increased in 357 obesity (Milsap et al 1984), there is an accompanying increased sensitivity to adrenal suppression. Therefore, there should not be an adjustment of prednisolone dosage in the obese patient.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Clinical Pharmacokinetics and Endocrine Disorders Therapeutic Implications

O’Connor

Feely

1987

Clinical Pharmacokinetics

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Endocrine disorders are common and produce widespread changes in cellular and organ function. Alterations in the sensitivity of patients with thyroid disorders to digoxin, anticoagulants and sedatives have been recognised for many years. Many of the recently documented kinetic alterations in endocrine patients are explicable on the basis of disease-induced changes in hepatic drug metabolism, protein binding and renal function. In hyperthyroidism the rate of absorption of paracetamol, propranolol and oxazepam is increased due to increased gastrointestinal motility. The volume of distribution of propranolol and digoxin is increased and there is decreased binding of both basic and acidic drugs as a consequence of alterations in alpha 1-acid glycoprotein and albumin concentration. The rate of glucuronidation of paracetamol and oxazepam is increased in hyperthyroidism. While oxidative metabolism of antipyrine, propranolol, metoprolol and theophylline is enhanced, the clearance of a number of other agents, including diazepam, warfarin, antithyroid drugs and phenytoin, is unaltered. The systemic clearance of propranolol is enhanced as a consequence of a 50% increase in liver blood flow. The rate of elimination of a number of endogenous substances, including cortisol, thyroid hormones and insulin, also appear to be enhanced. Hyperthyroidism has a variable effect on renal function, with a possible increase in digoxin elimination, but no effect on the clearance of renally excreted beta-blockers, atenolol, sotalol and nadolol. These kinetic changes suggest that individualization and higher than normal dosage of propranolol is necessary to control hyperthyroidism, and in thyrotoxic atrial fibrillation higher doses of digoxin or additional therapy with beta-blockers, or verapamil, may be indicated. The increased sensitivity of thyrotoxic patients to warfarin suggest care with dosage and frequent monitoring of response are warranted. Less information is available concerning hypothyroidism, but there is a general trend for decreased absorption of paracetamol and propranolol. In addition, the volume of distribution of digoxin is reduced, as is renal clearance. Limited studies suggest no alteration in the glucuronidation of oxazepam, but antipyrine clearance appears to be reduced. Steady-state propranolol concentrations are elevated in hypothyroidism and there appears to be a decreased metabolism of thyroid hormones and cortisol. Preliminary information suggests the binding of propranolol is increased. Thus, in the treatment of hypothyroid patients, a lower dosage of propranolol may be required.(ABSTRACT TRUNCATED AT 400 WORDS)

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“…We believe that the different BMI in the two groups did not confound the results. A higher bw is associated with an increase both in the volume of distribution and the clearance of steroids (19); thus, the net effect, if any, would be a diminished drug effectiveness.…”

Section: Discussionmentioning

confidence: 99%