We administered a "cocktail" of three model substrates for hepatic processes: antipyrine for oxidation, lorazepam for glucuronidation, and indocyanine green for hepatic blood flow, to children with acute lymphocytic leukemia (ALL). The plasma clearance of these substrates was determined before and after remission-induction therapy in 14 children with ALL. We found an improvement in clearance of antipyrine (0.65 to 0.95 ml/min/kg; P less than 0.01) and lorazepam (0.93 to 1.20 ml/min/kg; P less than 0.05) in 12 of 14 patients, with a mean increase of 67% and 52%, respectively, from before to after remission. There was no significant difference in mean indocyanine green clearance from before to after induction (14.8 vs. 14.4 ml/min/kg). There were no significant differences in liver function test results (SGOT, prothrombin time, or serum bilirubin) from before to after induction. Plasma concentrations of albumin, alpha 1-acid glycoprotein, and apolipoprotein A changed by a mean of +11.1%, -38.2%, and +68.6%, respectively, from before to after remission. However, these changes did not account for the changes in total plasma clearance of lorazepam, because lorazepam free fraction did not change and lorazepam free clearance increased by a mean of 83%. Our hypothesis is that eradication of hepatic leukemic infiltration by ALL remission therapy resulted in an improvement in microsomal metabolism of antipyrine and lorazepam.
Older patients are frequent users of aspirin and acetaminophen, either recommended by physicians or self‐prescribed, for the aches and pains that accompany aging. These mild analgesics provide effective pain relief when used appropriately. Aspirin and acetaminophen are equianalgesic on a milligram‐for‐milligram basis for most indications. Both are safe for most patients. Aspirin use may be associated with salicylate intoxication or salicylate interactions with other agents. There have been reports of an association of hepatotoxicity with acute massive overdosages of acetaminophen.
Theophylline kinetics after intravenous aminophylline were determined in 5 nonsmoking healthy males before and after allopurinol for 1 wk. There was no significant alteration in theophylline disposition.
The role of the clinical pharmacist in the institutional setting has been expanding at an ever increasing rate. His role as a clinical consultant with the rounding team has become firmly established. This is supplemented with rational product selection utilizing a hospital formulary. Both clinical pharmacokinetics and nutrition are services that benefit the patient directly in his inpatient environment. Toxicology and drug information provided directly to the consumer has also become accepted. Services provided to institution-wide committees allow a comprehensive understanding of the selection, delivery, and follow-up of medication administration to the patient. Many of these services described have become reimbursable by third-party carriers and other appropriate agencies. As other services are reimbursed, the role of the clinical pharmacist will expand beyond the limited scopes discussed in this paper.
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