Optimization of individual pharmacotherapy based on multiple evaluations of patient data

Abstract

To date, limited drug information is available for the individual optimization of pharmacotherapy. The author attempted multiple evaluations of patient data on factors related to the pharmacokinetics, drug efficacy, and adverse reactions observed in clinical settings. Through the clinical studies, drug information on the individual optimization of pharmacotherapy needed by health professionals including physicians and pharmacists was identified. Major findings were: 1) Cachectic cancer patients had high plasma concentrations of oxycodone via the reduction of CYP3A activity. The metabolic reduction in cachectic cancer patients was potentially related to the elevated serum level of interleukin-6. 2) Dopamine receptor D 2 (DRD2) genetic mutations and being female led to poor antiemetic efficacy of the treatment of opioid-induced nausea in prochlorperazine-treated patients. The opioid receptor μ1 (OPRM1) wild genotype in addition to being female and having high plasma concentrations of prochlorperazine increased prolactin secretion during oxycodone treatment. 3) Rheumatoid arthritis patients with a genetic mutation of ATP-binding cassette subfamily B member 1 (ABCB1) had high plasma concentrations of tacrolimus and its 13-O-demethylate. The ABCB1 genetic mutation and associated high plasma concentration of tacrolimus decreased kidney function. 4) Chronic inflammation increased the plasma voriconazole concentration via its poor metabolism, whereas it did not alter the plasma itraconazole concentration. Although co-administration of prednisolone did not affect the plasma concentration of triazole antifungals, it weakly increased voriconazole metabolism. 5) In breastfeeding women, the median milk/plasma concentration ratio of amlodipine was 0.85. However, the observed relative infant dose of amlodipine in most patients was less than 10%.