When optimizing pharmacotherapy for patients with renal dysfunction, the accurate renal excretion ratio (Rr) of the drug must be known. Rr is the ratio of renal drug clearance to total body drug clearance. The urinary excretion ratio of the unchanged drug (Xu/dose) is required to calculate Rr. Xu/dose is often calculated based on radioactivity excreted in the urine after administration of a radioisotope-labelled drug, taking into account the unmetabolized drug and inactive metabolites together. However, when a fraction of the metabolized drug is high, decreased renal function does not greatly affect the efficacy or safety. Xu/dose needs to be calculated based on the active unchanged drug. The Rr of oral drugs is calculated by Xu/dose divided by bioavailability. If the metabolites of a drug affect its efficacy or toxicity, it is necessary to consider the renal excretion of these metabolites when adjusting drug dosages. If a drug has a long half-life in blood, the evaluation of Xu/dose needs to consider the time required for the drug to be completely excreted from the body. Drug dosages and the frequency of drug administration are adjusted in patients with renal dysfunction to maintain the drug blood exposure comparable to that of patients with normal renal function. While decreasing drug dosages without altering the frequency is relatively simple, a steady drug concentration in the blood is only reached after a prolonged time. This steady state may be reached earlier if the drug is initially administered at a higher dosage. Adjusting the frequency without adjusting the dosage allows maximum and minimum blood concentrations to be modulated so that they are the same as those of patients with normal renal function. These various principles must be considered to effectively tailor drug administration in patients with kidney disease.
Most elderly people have a decreased glomerular filtration rate (GFR) as an indicator of renal function with increasing age, even if serum creatinine（ S-Cr） is within normal range. The decreased renal function of elderly people causes adverse reactions to increase the blood concentration of renaly excreted drugs. If pharmacists working in community pharmacies could simply and quickly evaluate renal function in elderly people who had been administrated renaly excreted drugs, they could help prevent adverse reactions and suggest an optimal dosage for doctor to prescribe, who have not received an evaluation of renal function in hospital and who do not bring laboratory examination results to a pharmacy. We practiced self-check of S-Cr in a long-term care health facility in preparation for practice in pharmacy.. We examined the prescriptions of 92 subjects, of who 22 subjects who were administered renaly excreted drugs practiced self-check of S-Cr. We estimated renal function (creatinine clearance: CCr) to measure S-Cr to collect blood from the prick of a finger with using of self-check S-Cr testing machine, Stat Sensor -I® (Nova Biomedical Inc). We examined the availability of self-check S-Cr test and relation between renal function and actual prescription of renaly excreted drugs for elderly people. The self-check of S-Cr via use of the Stat Sensor –I® was useful to estimate the renal function simply and quickly with the guidance of a pharmacist. Though S-Crs were in the normal range, elderly subjects of CCr less than 50 mL/min were 11 of 12 subjects (91.7%). 5 out of 22 subjects of the elderly subjects needed a reduction in dose (22.7%). These dosage for all subjects were reduced to approach a reduction of dose to prescribing doctor. S-Cr was not much examined in elderly patients, and even if examined, it was not used in elderly patients to adjust the optimal dosage as to renal function to calculate CCr or GFR. Many elderly patients had decreased renal function requiring a dose adjustment of renaly excreted drug. It is thought that among elderly patients taking renaly excreted drugs are absolutely necessary to estimate the renal function. In conclusion, we believe that self-check of S-Cr that can determine renal function simply and quickly is useful to adjust the dose of renaly excreted drugs. Further, we also believe that pharmacists working in community pharmacies could help prevent the adverse reactions through the use of the self-check of S-Cr in elderly patients.
When we argue about proper use of drugs, it is essential to set appropriate dose levels for individual patients. Paying attention to drugs which require dose adjustment in patients with compromised renal function, we selected 5 drugs (allopurinol, amantadine, cibenzoline, digoxin and disopyramide) for this multicenter study designed to investigate: (1) to which extent appropriate dose setting had been practiced on these drugs upon admission of individual patients; and (2) whether or not intervention by pharmacists into dose re-setting was possible when such intervention was needed. Of the 4596 patients studied, 280 carried any of the five drugs prescribed before admission. CKD stage was I in 10 cases and III or higher in 70% of these patients. When rated in accordance with the dose reduction criteria for patients with compromised renal function, the dose level was excessively high for amantadine in 61.5% of all cases, allopurinol in 19.2%, digoxin in 43.8% and cibenzoline in 46.2%. For 32.9% of all cases, dose reduction or discontinuation was implemented under intervention by pharmacists. These results suggest that dose level setting and checking for patients with compromised renal function were not satisfactory. From now on, it seems desirable to facilitate sharing of patients’ renal function data, including dispensing pharmacies, to enable more active intervention by pharmacists.