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%.

Antifungal Drugs TDM: Trends and Update

“…Inflammation has consistently been reported to contribute to high intrapatient and interpatient variability for VRZ. 155 An increase in VRZ trough levels (2- to 3-fold) due to a decrease in metabolism 145 is consistently reported, with CRP used as a marker of inflammation in both adults 156 and children over the age of 12 years 157 (not in infants 158 ). CRP has been identified as an independent determinant of VRZ trough levels, 159 but this study failed to incorporate the role of genetic status to inflammation on drug exposure.…”

“…ISZ dose was, therefore, increased to 200 mg •2 to achieve a target of 3.5 mg/L for Mucorales infection in a patient undergoing bariatric surgery. 144 Attention should be paid to cachexia in cancer patients, who are at risk of low levels of CYP3A4 activity due to possible interleukin genetic mutation 145 and VRZ underexposure due to anatomical and physiological changes, including mucosal atrophy. 146…”

“…339,340 Sources of PK variability (CYP2C19, age, and liver function) 341 are included in these models, and many DDIs have been identified, involving prednisolone, in particular. 145 High procalcitonin levels are associated with a risk of supratherapeutic levels after the loading dose, 342 and serum albumin levels affect VRZ levels. 110,171 Despite its efficacy, 343 frequent safety issues have been reported for VRZ.…”

“…Attention should be paid to cachexia in cancer patients, who are at risk of low levels of CYP3A4 activity due to possible interleukin genetic mutation 145 and VRZ underexposure due to anatomical and physiological changes, including mucosal atrophy. 146…”

Differences in Pharmaceutical Intervention Triggers for the Optimization of Medication by Patient Age: A University Hospital Study

“…Pharmacist interventions, such as comprehensive medication reviews, extraction of information related to the medication from medical records, interviews with the patient, assessment of the prescribed medicines, and making prescription changes or modification after discussion with physicians, can contribute to the reduction of medication-related harms. [6][7][8][9] Although additional, rigorously designed studies are required, several systematic reviews have provided evidence that pharmacists' interventions through medication review are effective in reducing hospital readmissions. [10][11][12][13][14] In Japan, the "Guidelines for Medical Treatment and Its Safety in the Elderly" was published and disseminated in 2015 from the Japan Geriatrics Society.…”