Journal of Antimicrobial Chemotherapy (1990) 26, Suppl. E, 29-34
Multiple dose pharmacokinetics of cefpodoxime in young adult and elderly patients C. Backhouse', A. Wade*, P. Williamson', D. Tremblay^ and B. Lenfant*
Multiple dose pharmacokinetics of a new third-generation cephalosporin, cefpodoxime, were evaluated in adults (15, 18-60 years) and elderly adults (10, ^ 7 0 years), all out-patients suffering from acute lower respiratory tract infection. A dose of 200 mg cefpodoxime proxetil (expressed in mg cefpodoxime) was administered 12hourly for seven to ten days and timed blood samples were evaluated on days 0, 3, 5, 6/7 and on the last day of treatment. Results showed that the pharmacokinetics in adult and elderly patients were comparable with those of healthy volunteers and with each other, with the exception of one elderly patient with severe renal impairment. Dosage adjustment of cefpodoxime proxetil does not therefore appear to be necessary in the elderly unless there is evidence of severe renal insufficiency. Introduction
Cefpodoxime is a new third generation cephalosporin, administered orally as an ester (cefpodoxime proxetil). Its in-vitro spectrum of activity makes it suitable for the treatment of infections of the respiratory tract, administered at a maximum dosage of 200 mg twice daily (Wise et al., 1990). Single dose kinetic studies in healthy volunteers indicate that the serum half life (Txr^ is approximately 2-4 h and that 80% of the absorbed dose is recovered in urine (Tremblay et al., 1990). Following administration of 200 mg cefpodoxime (as proxetil) the maximum serum concentration ( C ^ of 2-6 mg/1 is reached after about 2-5 h. The serum half-life is prolonged in renal dysfunction: in ten patients with crcatinine clearance between 10 and 39 ml/min, the mean of r1/2 was 7-67 h (data on file, Roussel Uclaf, France). Pharmacokinetic studies in a patient population have not yet been reported for cefpodoxime proxetil. This study was performed to determine the kinetic profile of cefpodoxime in adult and elderly adult patients suffering from respiratory tract infection and to compare it with that reported for volunteers. Patients and methods
Patients were considered for this study if they were 18-60 years or 70 years of age or older and reported to their general practitioner (GP) with signs and symptoms of an acute or acute on chronic respiratory tract infection, i.e. dyspnoea, chest signs, cough 29 0305-7453/90/26E029 + 06 $02.00/0
© 1990 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
•The Medical Centre, East Horsley, Surrey KT246QT, UK, bThe Health Centre, Clydebank, Glasgow, UK; 'Roussel Laboratories Limited, Denham, Middlesex UB95HB, UK; dRoussel Uclaf, Direction Recherches Sante, 93230 Romainville, France
30
C Backbonse et al Table I. Sampling times
Day of treatment 0 3 5 6/7 Last day (6-10)
Sampling schedule
Pharmacokinetic parameters
2 h after the first administration ] before (0-1 h) | administration of J morning dosage before the morning administration
AUC™
3, 4, 6 and 8 h 12 h after administration
T
cnh .
and sputum production. All patients had to produce purulent or mucopurulent sputum before recruitment. Patients with known penicillin hypersensitivity, severe renal or hepatic impairment or malabsorption syndrome or who were pregnant, lactating or at risk of becoming pregnant were excluded. No other antibiotic was prescribed and patients had not received antibiotic therapy within 72 h of admission to the study. All patients gave signed informed consent to enter this study for which ethics committee approval had been granted. Cefpodoxime proxetil was administered orally, as a dose equivalent to 200 mg active cefpodoxime, twice daily for six to ten days. Blood samples were collected at timed intervals as outlined in Table I. Blood samples for standard biochemical and haematological analysis were also taken before and after the trial.
Assay of cefpodoxime proxetil Plasma samples were temporarily stored at the GP Health Centre at — 20°C for a maximum of four weeks. Frozen samples were then transferred in solid CO 2 to Roussel for assay by high performance liquid chromatography ( H P L Q (Tremblay et al., 1990). Calibration range and control samples were prepared separately with pooled blank human plasma, spiked with a known concentration of cefpodoxime. The detection limit was 0-020 mg/1 for a sample size of 0-25 ml. The coefficients of variation of the control plasma were 5-8, 3-8 and 4-3% for cefpodoxime concentrations of 0-1, 0-5 and 2 0 mg/1 respectively. Samples were assayed in 13 batches, each comprising a calibration range, samples from two or three subjects and a control plasma (0-1, 0-5 or 2-Omg/l) after every ninth test sample.
Pharmacokinetic parameters Observed pharmacokinetic parameters were derived from data review and are defined in Table I. A U C o ^ h was calculated from the trapezoidal rule, and a bi-exponential function was fitted to the data to estimate the serum elimination half-life (Tlf2).
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
1h 2h
Multiple dose phannacokinetics
31
Creatinine clearance
Creatininc clearance was calculated according to the formula of Cockcroft & Gault (1976) as follows: creatinine clearance (ml/min) =
(140 - age) x weight (kg) 08 x serum creatinine (/nnol/1)
Statistical analysis
Results Twenty-six patients were recruited to the study. Twenty-five patients completed the trial satisfactorily and at the end of the treatment (median duration seven days) 23 had made a satisfactory clinical response. One patient withdrew because of a gastrointestinal disturbance and no data are presented for this case. Demographic data on the 25 evaluable patients who completed the study are shown in Table II. The weight, height and renal function varied greatly within each group, and, not surprisingly, moderate impairment of renal function was reported for many patients in the elderly group (Cla 54 ±7 ml/min). Serum biochemical tests on the eldest Table n . Demographic and renal function data Patients No. of patients Male/female Age* (Years) Weight* (kg) Height* (in) Urea' (mm/1) Creatinine" (/anol/1) Creatinine clearance* (ml/min)
young 15 7/8 41-4±2-8 26-57 671 ±3-2 43-89 l-68±O02 1 57-1-80 4-3 ± 0 3 2-7 82±4 62-118 103±6 54-160
elderly 9
1*
5/4 73-4 ±1-2 70-81 69-4 ±6-7 51-144 1-68±(K)3 1-56-1-85 6-6 ±0-5 5-9 114±12 81-195
1/0 85
1-59
54±7
22
57
14 176
89-29
"Values given are mean±s.E.M. and range. The data for the oldest patient are presented separately; his serum biochemistry indicated severe renal impairment and his pharmacokinetic parameters reflected this.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
Patient data were allocated to one of two groups according to age: group 1, 18-60 years and group 2, 70 years or greater. Two comparisons were made: within a group and between groups. Within a group, a two-way analysis of variance (ANOVA) was performed to assess the effect of time (taking inter-patient variability into account) on: C^ between the first and last dose, and Cmi,, between day 3, 5 and 6/7. ANOVA was performed to compare, between groups, the pharmacokinetic parameters of the young and elderly patients.
32
C. Backhouse et al. Table III. Pharmacolcinetic parameters of cefpodoxime following the last dose Parameters Q ^ o (mg/l) Cl2b (mg/l) C ^ (mg/l) AUQ.,,,, (mg/l.h) TV. (h)
(R - 15)
Elderly patients' (n = 9)
0-40±Oll 0-31±0-10 2-75 ±0-21 2-0510-20 15-011-3 2-5310-15
0-88 i O W 0-6410-10* 3-0510-24"* 2-6910-23' 20-611-6" 3-6510-31'
Young patients
patient at recruitment indicated previously undiagnosed, severe renal impairment; these data are therefore presented separately. The pharmacokinetic parameters (mean±s.E.M.) of cefpodoxime following the last dose are shown in Table III, and the C a and Cmia, 0 (mean±s.E.M.) cefpodoxime concentrations reported at intervals throughout treatment are shown in Tables IV and V respectively. The mean plasma concentration-time curves for the young and elderly patients are shown in Figure 1. Serum Tm and 7 ^ were prolonged in the elderly and C, a and AUCo_ia were increased (Table III). In addition, C ^ levels in the elderly were higher than those in the young patient group (Table V). However, there was no evidence of significant accumulation of cefpodoxime in either group: Cn and C ^ did not vary significantly between the first and last doses (Tables IV and V). Discussion The aim of this study was to examine the pharmacokinetics of cefpodoxime in a diverse population in a clinical setting. In this type of study, unfortunately, it is not possible to follow as rigorous a protocol as in healthy volunteer groups. In addition, a patient population will not conform with respect to weight, age and renal function. Nevertheless, the pharmacokinetic parameters reported in this study are very similar to those Table IV. Mean and standard deviations of the mean of the Cjt values '
Cj h (first dose) C 2h (last dose) ANOVA (effect of time)
Young patients (n-15)
Elderly patients (n = 8 /
ANOVA (effect of age)
2-1310-30 2-6410-23 NS
21510-18 2-5210-28 NS
NS NS
•Plasma concentrations of cefpodoxime (mg/l) observed: 2 h after the first dote administered (day 0) and 2 h after the last dose (last day). 'Analysis performed on complete data sets only. ANOVA, analysts of variance. NS, P > 0-05.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
T h e parameters of the oldest patient are excluded and for Cml^0, Cut and (?„„, were 2-69, 218 and 6-35 mg/l respectively, T,, wai 8 h and AUC „.„. was 55-1 mg/l.h. Analysis of variance between groups: "P > 005, not significant; *O05 > P > 0-01; •0-01 > />>(H)01.
Multiple dose pharmacoklnetks
33
Table V. Mean and standard deviations of the mean of the C,,,^,, values' Elderly patients
Young patients (it = 1 3 ) *
(day 3) (day 5) 'mm.0 (day 6/7) ANOVA (effect of time)
0-41 ±0-08 O43±(M)5 0.48±0-10 NS
0-81 ± 0 1 3 ' 0-83 ±0-08' NS
previously reported in adult and elderly adult healthy volunteers (Tremblay et al., 1990). For each group there was no significant difference between the 2 h concentrations measured after the first and last dose, nor between the minimum concentrations measured on the first day, day 3, day 5 and day 6/7. Steady state was attained without notable accumulation in either the adult or the elderly adult group. The elimination half-life was longer in the elderly, resulting in a higher C^, approximately twice that recorded for the adult group. However, the serum half-life was always less than 4 li—much shorter than the recommended dosing interval of 12 h. Thus, in the elderly, the serum half-life of cefpodoxime, although prolonged, was still low enough to prevent notable accumulation. It is known that cefpodoxime excretion is predominantly renal: approximately 80% of the absorbed dose is excreted in urine (Tremblay et al., 1990). The cefpodoxime pharmacokinetic parameters for the patient with severe renal impairment (C/CT
1
2
3
4
6 Tlmt (h)
e
12
Fignre 1. Mean and standard deviation plasma concentration-time curves for cefpodoxhne in young ( • ) and elderly (O) patients after last morning dose.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
"Plasma concentrations of cefpodoxime (mg/1) observed: before morning dose on day 3, day 5 and day 6/7. 'Analysis performed on complete data sets only. Analysis of variance between groups: NS, P > 005; tHJS > P > 0-01; iO-01 > P> 0001; 'P< 0001.
34
C. Backhouse et al
References Cockcroft, D. W. & Gault, M. H. (1976). Prediction of crcatinine clearance from serum creatinine. Nephron 16, 31-41. Tremblay, D., Dupront, A., Ho, C , Coussediere, D. & Lenfant, B. (1990). Pharmacokinetics of cefpodoxime in young and elderly volunteers after single doses. Journal of Antimicrobial Chemotherapy 26, Suppl. E, 21-fi. Wise, R., Andrews, J. M., Ashby, J. P. & Thornber, D. (1990). The in-vitro activity of cefpodoxime: a comparison with other oral cephalosporins. Journal of Antimicrobial Chemotherapy 25, 541-50.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
22 ml/min) were markedly different from those of the other patients studied, but were similar to those previously reported in ten volunteers with renal insufficiency (Cla 10-39 ml/min; Tm, 7-67 h; AUCVash. 77-8 mg/1, data on file at Roussel Uclaf, France). This patient can thus be considered as a special case; the serum elimination half-life was 8 h and the cefpodoxime concentrations measured around the last dose were approximately double the means of those recorded for the other patients in the elderly group. It can be concluded that, although the pharmacokinetic parameters of cefpodoxime are slightly modified in the elderly, these minor variations can be attributed to the mild renal impairment associated with old age. These data confirm those previously reported for healthy volunteers, and dosage adjustment of cefpodoxime is not likely to be necessary unless there is evidence of severe renal insufficiency.
Multiple dose pharmacokinetics of cefpodoxime in young adult and elderly patients C. Backhouse', A. Wade*, P. Williamson', D. Tremblay^ and B. Lenfant*
Multiple dose pharmacokinetics of a new third-generation cephalosporin, cefpodoxime, were evaluated in adults (15, 18-60 years) and elderly adults (10, ^ 7 0 years), all out-patients suffering from acute lower respiratory tract infection. A dose of 200 mg cefpodoxime proxetil (expressed in mg cefpodoxime) was administered 12hourly for seven to ten days and timed blood samples were evaluated on days 0, 3, 5, 6/7 and on the last day of treatment. Results showed that the pharmacokinetics in adult and elderly patients were comparable with those of healthy volunteers and with each other, with the exception of one elderly patient with severe renal impairment. Dosage adjustment of cefpodoxime proxetil does not therefore appear to be necessary in the elderly unless there is evidence of severe renal insufficiency. Introduction
Cefpodoxime is a new third generation cephalosporin, administered orally as an ester (cefpodoxime proxetil). Its in-vitro spectrum of activity makes it suitable for the treatment of infections of the respiratory tract, administered at a maximum dosage of 200 mg twice daily (Wise et al., 1990). Single dose kinetic studies in healthy volunteers indicate that the serum half life (Txr^ is approximately 2-4 h and that 80% of the absorbed dose is recovered in urine (Tremblay et al., 1990). Following administration of 200 mg cefpodoxime (as proxetil) the maximum serum concentration ( C ^ of 2-6 mg/1 is reached after about 2-5 h. The serum half-life is prolonged in renal dysfunction: in ten patients with crcatinine clearance between 10 and 39 ml/min, the mean of r1/2 was 7-67 h (data on file, Roussel Uclaf, France). Pharmacokinetic studies in a patient population have not yet been reported for cefpodoxime proxetil. This study was performed to determine the kinetic profile of cefpodoxime in adult and elderly adult patients suffering from respiratory tract infection and to compare it with that reported for volunteers. Patients and methods
Patients were considered for this study if they were 18-60 years or 70 years of age or older and reported to their general practitioner (GP) with signs and symptoms of an acute or acute on chronic respiratory tract infection, i.e. dyspnoea, chest signs, cough 29 0305-7453/90/26E029 + 06 $02.00/0
© 1990 The British Society for Antimicrobial Chemotherapy
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
•The Medical Centre, East Horsley, Surrey KT246QT, UK, bThe Health Centre, Clydebank, Glasgow, UK; 'Roussel Laboratories Limited, Denham, Middlesex UB95HB, UK; dRoussel Uclaf, Direction Recherches Sante, 93230 Romainville, France
30
C Backbonse et al Table I. Sampling times
Day of treatment 0 3 5 6/7 Last day (6-10)
Sampling schedule
Pharmacokinetic parameters
2 h after the first administration ] before (0-1 h) | administration of J morning dosage before the morning administration
AUC™
3, 4, 6 and 8 h 12 h after administration
T
cnh .
and sputum production. All patients had to produce purulent or mucopurulent sputum before recruitment. Patients with known penicillin hypersensitivity, severe renal or hepatic impairment or malabsorption syndrome or who were pregnant, lactating or at risk of becoming pregnant were excluded. No other antibiotic was prescribed and patients had not received antibiotic therapy within 72 h of admission to the study. All patients gave signed informed consent to enter this study for which ethics committee approval had been granted. Cefpodoxime proxetil was administered orally, as a dose equivalent to 200 mg active cefpodoxime, twice daily for six to ten days. Blood samples were collected at timed intervals as outlined in Table I. Blood samples for standard biochemical and haematological analysis were also taken before and after the trial.
Assay of cefpodoxime proxetil Plasma samples were temporarily stored at the GP Health Centre at — 20°C for a maximum of four weeks. Frozen samples were then transferred in solid CO 2 to Roussel for assay by high performance liquid chromatography ( H P L Q (Tremblay et al., 1990). Calibration range and control samples were prepared separately with pooled blank human plasma, spiked with a known concentration of cefpodoxime. The detection limit was 0-020 mg/1 for a sample size of 0-25 ml. The coefficients of variation of the control plasma were 5-8, 3-8 and 4-3% for cefpodoxime concentrations of 0-1, 0-5 and 2 0 mg/1 respectively. Samples were assayed in 13 batches, each comprising a calibration range, samples from two or three subjects and a control plasma (0-1, 0-5 or 2-Omg/l) after every ninth test sample.
Pharmacokinetic parameters Observed pharmacokinetic parameters were derived from data review and are defined in Table I. A U C o ^ h was calculated from the trapezoidal rule, and a bi-exponential function was fitted to the data to estimate the serum elimination half-life (Tlf2).
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
1h 2h
Multiple dose phannacokinetics
31
Creatinine clearance
Creatininc clearance was calculated according to the formula of Cockcroft & Gault (1976) as follows: creatinine clearance (ml/min) =
(140 - age) x weight (kg) 08 x serum creatinine (/nnol/1)
Statistical analysis
Results Twenty-six patients were recruited to the study. Twenty-five patients completed the trial satisfactorily and at the end of the treatment (median duration seven days) 23 had made a satisfactory clinical response. One patient withdrew because of a gastrointestinal disturbance and no data are presented for this case. Demographic data on the 25 evaluable patients who completed the study are shown in Table II. The weight, height and renal function varied greatly within each group, and, not surprisingly, moderate impairment of renal function was reported for many patients in the elderly group (Cla 54 ±7 ml/min). Serum biochemical tests on the eldest Table n . Demographic and renal function data Patients No. of patients Male/female Age* (Years) Weight* (kg) Height* (in) Urea' (mm/1) Creatinine" (/anol/1) Creatinine clearance* (ml/min)
young 15 7/8 41-4±2-8 26-57 671 ±3-2 43-89 l-68±O02 1 57-1-80 4-3 ± 0 3 2-7 82±4 62-118 103±6 54-160
elderly 9
1*
5/4 73-4 ±1-2 70-81 69-4 ±6-7 51-144 1-68±(K)3 1-56-1-85 6-6 ±0-5 5-9 114±12 81-195
1/0 85
1-59
54±7
22
57
14 176
89-29
"Values given are mean±s.E.M. and range. The data for the oldest patient are presented separately; his serum biochemistry indicated severe renal impairment and his pharmacokinetic parameters reflected this.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
Patient data were allocated to one of two groups according to age: group 1, 18-60 years and group 2, 70 years or greater. Two comparisons were made: within a group and between groups. Within a group, a two-way analysis of variance (ANOVA) was performed to assess the effect of time (taking inter-patient variability into account) on: C^ between the first and last dose, and Cmi,, between day 3, 5 and 6/7. ANOVA was performed to compare, between groups, the pharmacokinetic parameters of the young and elderly patients.
32
C. Backhouse et al. Table III. Pharmacolcinetic parameters of cefpodoxime following the last dose Parameters Q ^ o (mg/l) Cl2b (mg/l) C ^ (mg/l) AUQ.,,,, (mg/l.h) TV. (h)
(R - 15)
Elderly patients' (n = 9)
0-40±Oll 0-31±0-10 2-75 ±0-21 2-0510-20 15-011-3 2-5310-15
0-88 i O W 0-6410-10* 3-0510-24"* 2-6910-23' 20-611-6" 3-6510-31'
Young patients
patient at recruitment indicated previously undiagnosed, severe renal impairment; these data are therefore presented separately. The pharmacokinetic parameters (mean±s.E.M.) of cefpodoxime following the last dose are shown in Table III, and the C a and Cmia, 0 (mean±s.E.M.) cefpodoxime concentrations reported at intervals throughout treatment are shown in Tables IV and V respectively. The mean plasma concentration-time curves for the young and elderly patients are shown in Figure 1. Serum Tm and 7 ^ were prolonged in the elderly and C, a and AUCo_ia were increased (Table III). In addition, C ^ levels in the elderly were higher than those in the young patient group (Table V). However, there was no evidence of significant accumulation of cefpodoxime in either group: Cn and C ^ did not vary significantly between the first and last doses (Tables IV and V). Discussion The aim of this study was to examine the pharmacokinetics of cefpodoxime in a diverse population in a clinical setting. In this type of study, unfortunately, it is not possible to follow as rigorous a protocol as in healthy volunteer groups. In addition, a patient population will not conform with respect to weight, age and renal function. Nevertheless, the pharmacokinetic parameters reported in this study are very similar to those Table IV. Mean and standard deviations of the mean of the Cjt values '
Cj h (first dose) C 2h (last dose) ANOVA (effect of time)
Young patients (n-15)
Elderly patients (n = 8 /
ANOVA (effect of age)
2-1310-30 2-6410-23 NS
21510-18 2-5210-28 NS
NS NS
•Plasma concentrations of cefpodoxime (mg/l) observed: 2 h after the first dote administered (day 0) and 2 h after the last dose (last day). 'Analysis performed on complete data sets only. ANOVA, analysts of variance. NS, P > 0-05.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
T h e parameters of the oldest patient are excluded and for Cml^0, Cut and (?„„, were 2-69, 218 and 6-35 mg/l respectively, T,, wai 8 h and AUC „.„. was 55-1 mg/l.h. Analysis of variance between groups: "P > 005, not significant; *O05 > P > 0-01; •0-01 > />>(H)01.
Multiple dose pharmacoklnetks
33
Table V. Mean and standard deviations of the mean of the C,,,^,, values' Elderly patients
Young patients (it = 1 3 ) *
(day 3) (day 5) 'mm.0 (day 6/7) ANOVA (effect of time)
0-41 ±0-08 O43±(M)5 0.48±0-10 NS
0-81 ± 0 1 3 ' 0-83 ±0-08' NS
previously reported in adult and elderly adult healthy volunteers (Tremblay et al., 1990). For each group there was no significant difference between the 2 h concentrations measured after the first and last dose, nor between the minimum concentrations measured on the first day, day 3, day 5 and day 6/7. Steady state was attained without notable accumulation in either the adult or the elderly adult group. The elimination half-life was longer in the elderly, resulting in a higher C^, approximately twice that recorded for the adult group. However, the serum half-life was always less than 4 li—much shorter than the recommended dosing interval of 12 h. Thus, in the elderly, the serum half-life of cefpodoxime, although prolonged, was still low enough to prevent notable accumulation. It is known that cefpodoxime excretion is predominantly renal: approximately 80% of the absorbed dose is excreted in urine (Tremblay et al., 1990). The cefpodoxime pharmacokinetic parameters for the patient with severe renal impairment (C/CT
1
2
3
4
6 Tlmt (h)
e
12
Fignre 1. Mean and standard deviation plasma concentration-time curves for cefpodoxhne in young ( • ) and elderly (O) patients after last morning dose.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
"Plasma concentrations of cefpodoxime (mg/1) observed: before morning dose on day 3, day 5 and day 6/7. 'Analysis performed on complete data sets only. Analysis of variance between groups: NS, P > 005; tHJS > P > 0-01; iO-01 > P> 0001; 'P< 0001.
34
C. Backhouse et al
References Cockcroft, D. W. & Gault, M. H. (1976). Prediction of crcatinine clearance from serum creatinine. Nephron 16, 31-41. Tremblay, D., Dupront, A., Ho, C , Coussediere, D. & Lenfant, B. (1990). Pharmacokinetics of cefpodoxime in young and elderly volunteers after single doses. Journal of Antimicrobial Chemotherapy 26, Suppl. E, 21-fi. Wise, R., Andrews, J. M., Ashby, J. P. & Thornber, D. (1990). The in-vitro activity of cefpodoxime: a comparison with other oral cephalosporins. Journal of Antimicrobial Chemotherapy 25, 541-50.
Downloaded from http://jac.oxfordjournals.org/ at New York University on April 24, 2015
22 ml/min) were markedly different from those of the other patients studied, but were similar to those previously reported in ten volunteers with renal insufficiency (Cla 10-39 ml/min; Tm, 7-67 h; AUCVash. 77-8 mg/1, data on file at Roussel Uclaf, France). This patient can thus be considered as a special case; the serum elimination half-life was 8 h and the cefpodoxime concentrations measured around the last dose were approximately double the means of those recorded for the other patients in the elderly group. It can be concluded that, although the pharmacokinetic parameters of cefpodoxime are slightly modified in the elderly, these minor variations can be attributed to the mild renal impairment associated with old age. These data confirm those previously reported for healthy volunteers, and dosage adjustment of cefpodoxime is not likely to be necessary unless there is evidence of severe renal insufficiency.
