日本化学療法学会雑誌第51巻第2号

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1 piperacillin piperacillin PIPC. g Cmax CL PIPC CL CLR CLNR CL PIPC g g Cmax PIPC Key words: piperacillin Piperacillin PIPC PIPC g g PIPC Cmax g g ml g g ml g g ml T T T PIPC g g T Ccr ml min AUCCmax PIPC g

2 PIPC I g piperacillin sodium g : : Body mass index B. M. I kg m B. M. I: kg m AST GOTALT GPTAl P GTP BUN Ccr : ml min : ml min HIV HBV HCV PIPC PIPC GCP PIPC. g ml PIPC desethyl Sampling Before dosing Time after administration h.. Blood Urine Affirmative Fig. Schedule of sampling for blood and urine.

3 Dosing Before After days after within days Back ground Signs and symptoms Physical examination Clinical examination Subjective symptoms Affirmative Fig. Schedule for examination. piperacillin DEt PIPC : ml rpm ml : ml Fig Fig PIPC Cmax CL PIPC AUC T MRTCLR Vdss desethyl piperacillin DEt PIPC GPMSP GCP WinNonlin ver.. SAS ver.. II Ccr Table

4 PIPC Table Subject profiles Age years Weight kg screening Ccr ml min pre Table Plasma concentration of piperacillin in elderly and non elderly volunteers after single drip infusion Concentration µg ml before h h h h h h h h h :Notdetected µg ml.. Ccr Ccr. ml mim ml mim BUN mg dls. mg dl Ccr ml min ml mim BUN mg dls. mg dl Table PIPCTable DEt PIPC Fig PIPC DEt PIPC Table PIPCTable DEt PIPC PIPC DEt PIPC PIPC DEt PIPC

5 Table Plasma concentration of desethyl piperacillin in elderly and non elderly volunteers after single drip infusion of piperacillin Concentration µg ml before h h h h h h h h h :Notdetected µg ml. piperacillin elderly non elderly elderly desethyl piperacillin non elderly n,. Time h Fig. Plasma concentrations of piperacillin and desethyl piperacillin in elderly and non elderly volunteers after single drip infusion of piperacillin. PIPC Table Cmax:. ml. ml CL: ml min ml min CL AUC:. h ml. h ml AUC T :. h. h T. h MRT:. h. h MRT. h CLR: ml min ml min CLNR CL CLR ml min ml min Vdss:. L. L

6 PIPC Table Urinary concentration of piperacillin in elderly and non elderly volunteers after single drip infusion Concentration µg ml h h h h h h h :Notdetected µg ml Table Urinary concentration of desethyl piperacillin in elderly and non elderly volunteers after single drip infusion of piperacillin Concentration µg ml h h h h h h h :Notdetected µg ml DEt PIPC Table Cmax:. ml. ml AUC:. h ml. h ml T :. h. h. h MRT:. h. h. h Tmax:. h. h

7 Table Pharmacokinetic parameters of piperacillin in elderly and non elderly volunteers after single drip infusion Cmax µg ml CL AUC ml min µg h ml T h MRT h CLR ml min Vdss L AUC µg h ml Table Pharmacokinetic parameters of desethyl piperacillin in elderly and non elderly volunteers after single drip infusion of piperacillin Cmax µg ml AUC µg h ml T h MRT h Tmax h Fig PIPC..DEt PIPC... PIPC PIPC CLR CL Vdss Ccr CLR CL Vdss Ccr CLR: CLR Ccr : p. : p=. Ccr: p=. CLR Ccr CLR Table CL: Ccr CL : p. Ccr: p=. : p=. CL Ccr CL

8 PIPC Cumulative recovery of piperacillin piperacillin elderly non elderly desethyl piperacillin elderly non elderly n, Fig. Urinary excretions of piperacillin and desethyl piperacillin in elderly and non elderly volunteers after single drip infusion of piperacillin. Cumulative recovery of DEt piperacillin Table CLR multiple regression on weight, age and Ccr Table Vdss multiple regression on weight, age and Ccr Variance Degrees of freedom Sum of squares Mean square F P Variance Degrees of freedom Sum of squares Mean square F P Weight Age Ccr Error Weight Age Ccr Error Total Total Table CL multiple regression on weight, age and Ccr Degrees of Sum of Mean Variance freedom squares square F P Weight Age Ccr Error Total Table Vdss: : p=. : p=. Ccr: p=. Table PIPC g Fig PIPC C ss max g C ss max C ss min ml. ml ml. ml C ss min g C ss max C ss min ml. ml ml. ml NOS.. III PIPC

9 g /day days elderly non elderly n C ss max at steady state in elderly:.. g/ml C ss max at steady state in non elderly:.. g/ml g /day days elderly non elderly n C ss max at steady state in elderly:.. g/ml C ss max at steady state in non elderly:.. g/ml g /day days elderly non elderly n C ss max at steady state in elderly:.. g/ml C ss max at steady state in non elderly:.. g/ml g /day days elderly non elderly n C ss max at steady state in elderly:. g/ml C ss max at steady state in non elderly:. g/ml g /day days elderly non elderly n C ss max at steady state in elderly:. g/ml C ss max at steady state in non elderly:. g/ml g /day days elderly non elderly n C ss max at steady state in elderly:. g/ml C ss max at steady state in non elderly:. g/ml g /day days elderly non elderly n C ss max at steady state in elderly:. g/ml C ss max at steady state in non elderly:. g/ml Fig. Simulated plasma concentrations of piperacillin in elderly and non elderly volunteers calculated from the parameters of single drip infusion.

10 PIPC Cmax CL CLR CL CLNR TMRT Vdss PIPC CL Vdss T CLR CLNR CL PIPC DEt PIPC DEt PIPC Cmax AUC T. PIPC CLR CL Vdss Ccr CLR CL Vdss Ccr CLR CL CLR Ccr CL CLR CLR Ccr CL CLR Ccr CL CLR Ccr Vdss PIPC PIPC CLR CL CL CLR Ccr PIPC PIPC Cmax AUC CL CLR CLNR Cmax CL T : Ccr: ml mim Ccr:. ml mim g g PIPC g PIPC Ccr : T Jpn. J. Antibiotics : : Piperacillin g gjpn. J. Antibiotics : : T Piperacillin Chemotherapy : Morrison J A Dornbush A C Sathe S S et al.: Pharmacokinetics of piperacillin sodium in patients with various degrees of impaired renal function. Drugs Exptl. Clin. Res.: : Tazobactam Piperacillin Chemotherapy S : : Tazobactam Piperacillin Chemotherapy S : : gatifloxacin S :

11 Piperacillin sodium pharmacokinetics in the elderly Kouya Shiba Jikei University School of Medicine Divisions of Internal Medicine and Infectious Disease Control Nishi Shinbashi Minatoku Tokyo Japan Piperacillin sodium PIPC was administered by intravenous drip to elderly nand non elderly n subjects at a dose of. g over a min period to determine the drug s pharmacokinetics Analysis based on pharmacokinetic found the following: The peak plasma concentration Cmax in the elderly tended to be higher than in the non elderly but not significantly. Systemic clearance CL in the elderly was lower than in the non elderly, was age related, and tendedtodecrease with age. Renal CLR and non renal CLNR clearance tended to decrease with age as with CL indicating that PIPC elimination through renal and non renal pathways decreased with age. Accumulation is not anticipated in either group under a regimen of g of PIPC times daily or g twice daily. In the elderly, Cmax tended to be higher and CL lower than in the non elderly. Dosages in this study showed no accumulation in either group indicating that similar dosages can be used in the elderly and non elderly. In the elderly, however the decreased PIPC elimination externally appears to be age related, requiring that doses be reduced in some patients.

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