Pharmacokinetics of Cloxacillin in Patients on Chronic Intermittent Haemodialysis and in Healthy Subjects

Abstract

Elimination and absorption of orally administered cloxacillin (Orbenin) was studied in 11 patients on chronic intermittent haemodialysis and 11 healthy subjects. For the patients, the mean value of the elimination rate constant was 0.31 h^-1 (T ½ = 2¼ h). Haemodialysis had no detectable effect on the elimination rate. The value found for the normals (1.21 h^-1; T½ = 34 min) is in accordance with the data in the literature. The extrarenal elimination rate in normals corresponds with the total elimination rate in patients without kidney function. In 6 of our patients the mean value of the absorption after oral administration of 1 g was 61% of the administered dose. The reliability of the method used to determine absorption in anuric patients from serum concentrations was verified by experiments in healthy subjects in whom absorption could also be estimated, on the basis of renal excretion. Our method proved to be reliable if certain reservations are taken into account. On the basis of the data obtained, we consider it advisable to give the same dosages of cloxaciUin to anuric patients as to patients with normal kidney function.

Effect of Probenecid on the Apparent Volume of Distribution and Elimination of Cloxacillin

“…In three of these patients, who were on hemodialysis, cloxacillin was infused at a rate of 0.6 g/h for 4 h. For the fourth patient, the only one with a partially disturbed kidney function, the cloxacillin was infused at a rate of 1 The apparent volume of distribution of cloxacillin during the continuous infusion can be calculated with the following equation (10): (2) in which A, is the amount administered up to time t, V is the apparent volume of distribution, C, is the concentration at time t, K is the elimination rate constant, and fC' C -dt is the area under the serum concentration curve from time zero to time t. A linear relationship exists between A, and the righthand part of the equation; the slope is equal to V. Table 1 shows the calculated values of the apparent volume of distribution (V) of cloxacillin, given without or together with probenecid. The mean value for the elimination rate constant of cloxacillin in anuric patients (0.326/h) is in close accordance with the value we obtained in anuric patients after a single intravenous injection (9). Tables 2 to 4 give the serum concentrations in each individual patient.…”

“…For this purpose we chose patients lacking kidney function, because under this condition an indirect effect on the apparent volume of distribution by probenecid via a reduced elimination is excluded. The penicillin chosen was cloxacillin, because we were familiar with the pharmacokinetics of this drug in patients without renal function (9).…”

Pharmacokinetics of flucloxacillin and cloxacillin in healthy subjects and patients on chronic intermittent haemodialysis.

“…0.25-0.5,ug/ml. A major disadvantage is, however, the rather poor and variable absorption after oral administration to healthy volunteers and patients on chronic intermittent haemodialysis (Nauta, Mattie & Goslings, 1973).…”

“…In addition, the same parameters were applied to investigate flucloxacillin in patients on chronic intermittent haemodialysis, for comparison with our earlier findings of cloxacillin in this type of patient (Nauta et aL, 1973).…”

The passage of cloxacillin into cerebrospinal fluid in the absence of meningitis.

“…Pharmacokinetic parameters describing plasma drug concentrations in the remaining nine subjects are shown in Table 1. The mean value of 0.95 h-1 for k was lower than the value of 1.21 h-1 found earlier for healthy volunteers [11]. Plasma protein binding ranged from 54% to 89% and the albumin quotient ranged from 3.9 to 23.0, seven values being slightly elevated above the normal value of 7 or less [6].…”