病態変動に伴う薬物の血漿中濃度変動パターンを推定する簡易ソフトの開発
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概要
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We developed easy-to-use software based on Microsoft Excel in order to predict qualitative changes in drug concentration in plasma-time profiles due to changes in patients' clinical conditions and obtain information for determining optimal dosage regimens.We selected 443 therapeutic agents that are widely used in patients and examined 7 pharmacokinetic parameters in healthy volunteers for each of the drugs selected : bioavailability (F ), percentage of drug dose excreted unchanged into the urine (Ae ), fraction of drug not bound to serum protein (fp ), total clearance (CLtot ), volume of distribution (Vd ), biological half life (t1/2 ) and time of occurrence of highest plasma drug concentration following administration (tmax ). The drugs were then categorized according to elimination route (renal excretion or hepatic metabolism), high or low percentage extraction by the kidneys/liver, extent of protein binding (protein-binding sensitive or not) and large or small volume of distribution, and the drugs were tabulated by the software using these pharmacokinetic parameters.Next, typical time courses of the plasma concentration of each category of drugs and their unbound fractions were created by the software for 4 types of administration : bolus intravenous injection, constant intravenous infusion, and single and repeated oral administration. The software was also used to infer typical time courses for plasma concentrations due to 4 assumed changes in clinical conditions (1. increase in fp , 2. decrease in intrinsic renal or hepatic clearance, CLint,x , 3. decrease in renal or hepatic blood flow, Qx , 4. increase in fp with a decrease in Qx ) based on the general name of brand name for the drugs that were input.The software we developed indicated that the elimination pharmacokinetics of about 80% of the selected drugs depended on renal excretion or hepatic metabolism and it was effective in creating plasma concentration-time profiles due to changes in clinical conditions. It should therefore be a useful tool for pharmacists in hospitals and community pharmacies.
- 日本医療薬学会の論文
日本医療薬学会 | 論文
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