Pharmacokinetics of cefotaxime in healthy volunteers and patients

armacy (K.B.P., D.P.N.) and Diseases @*P.N., R.Q.), and Office for Research(U-LPI.), IXarBford !saool of mamasy (KELP., .P.N., C.H.N.), tiWPsilY Connecticut, Stows; and School of Me of CQnnecticul, Famti@on, Cormecticcut,USA.

SSDI 0

0 I

discussed.

dose of cefota~me

serum concentrations, th (AUC) achieved by IV and

C,, of 125.8 2 19.2 p&nl for cefot~ime and 10.1 -L 1.8 t.~g/mlat PI’,, of OS-O.66 h for desacetyl-cefotaxime (VallCe et al., 1991). The reported AUCs for the parent and metabolite in this investigation were 141.9 +- 30.7 and 39.1 zk 7.4 pg - h/ml, respectiv The apparent difference in the AUCs between

ere was a non-

AUC with increasing dose. III addition, upon mulGpIe-doSe administration, accumulation of drug did not occurwith cefotaxime or its metabolite. (Braga et al., 1982; Neu et al., 1980)

Pharmacokinetics of Cefot e an Desacetyl-cefotaxime in Healthy Volunteers After a I-g IV Bolus of Cefot~~imea

Gna,b4w! Vd (liters/l.73 In?) Tv~(W Cl (Inhin) Protein binding (%)

41.1 .3 33.3 1.1 138.4 27-38

“IV,intravenous;AUC, area under the curve.

7.9 12.5 1.5 243.6 -

~sa&ybcefcWdme is more by renal dysfunction, with an half-life from 1.5 in healthy v0 ml/mm) and up to 10 et al., 1982; Wise et al., use et al. (1981) showed that in

cause limited data are available. The ~barmac0~inetics of cefotaxime in acutely ill elderly patients was assessed by Jonsson and Walker (1986). patients with varying renal and circulatory Sta were administered cefotaxime IV 1 g every 12

aSs. The most chnicahy Significant change is a decrease in renal function, which for an icrobials that are primarily eliminated by the kidneys will sitIy alter the half-life of the drug. Ludwig et ai. reported an increase in the half-life of cefotaxime with age-related decreases in creati tients over 80 years of age ( , the half-ale of cef0ta~ that 0f desacetykefots may require dosage increasing the dosing interval to every 12 h. AS a result of the prolongation in the haMtie, dosage adjustment of cefotaxime is necessary in patients with impaired renal function. Because the volume of distribution is not affected by renal impairment, the dose remains the same; however, the dosing interval will increase with decreasing renal functioaa. Patients with Ucr of >30 ml/mm need not

tion unless concomitant

as bee

aW cal s

ctious TABLE 3 Dosage Adj~s~ent Renal Impairment

in

Rosage Guidelines >30 m-30 Cl0

lgevery8h 1 g every B-12 h 0.5-l g every 12-24 h

1

al a

P

_ ..._................... ..._ .._., _,...._,....

.......

_. ___ . ._.. .

0.4

Q

40

2

e

in nomd

42

and i

44

, or 12 h. Patients who recerve

information regarding the patien which would significantly increase

Clin Ther 569-78. Chodo? J, Francke EL, Sahzman M, Neu I-IC macoi inetics of intravenous cefotaxime in dergoing chronic hemodialysis. Ther Brug ene~a~on

Aswapokee p, Ho I, macokinetics of cefotaxime. ckemot??t?r16z592-597. Goldstein EJC, Cherubin C

into

Fu

Anti~i~r~~ Agents

Biqn vitriol Infat Dis lZ:lQl-105. %minger W, UihIein M, Perenci p, Moser C, Ceorgop0~10s (1984) Cefotaxime and desacetyl-cefotaxime levels in hepatic dysfunction. 1 Antimicrob th.er lQ(Supp1 B):143-146. I-&mm D (1981) Susceptibility of penicillin insensitive ~~e$t~m to new cephalosporim. Drugs22(Suppl

:

Neu WC (1982) Antibacteriai activity of desacetyl cefotaxcombination with cefotaxime. Reu In-

tin&rob Agents Chemother 15:27%28P.

Jo-n M WalcierM (1986) Pharmacokinetics of intravenous antibioticsin acutely iII elderly patients. EUPJ Clin -15:62%83.

Neu WC, Fu tics a (1988) muscular injection of single and multipIe doses Clin Pharrmacol l-her 22677-685. Oiimi K, Hayashi I, Aonuma S, Konno K (1988) In vitro activity of desacetylcefotaxime and the interaction with

55