Single-dose ceftriaxone kinetics in functionally anephric patients

Stoeckel, Klaus; Hoppe-Seyler, G.; Blumberg, A; Keller, E.

doi:10.1038/clpt.1983.86

Cited by 39 publications

(16 citation statements)

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“…The broken lines represent the average concentration-time profiles of ceftriaxone in plasma after intravenous infusion of a 1-g dose for healthy young (---; n = 8) and elderly (--; n = 8) subjects with normal renal function. those of Cohen et al (3) and Stoeckel et al (14). These investigators concluded from their data that no changes in the dosage regimen of ceftriaxone would be required for endstage renal disease patients with normal hepatic function.…”

Section: Discussionsupporting

confidence: 50%

“…A substantially prolonged half-life of ceftriaxone in a small percentage of dialysis patients was also observed by may be due to an impaired biliary excretion process, which is the alternate pathway of elimination for ceftriaxone in humans (12)(13)(14). It is suggested, therefore, that ceftriaxone concentrations in plasma should be monitored in the patients with end-stage renal disease to determine whether dosage adjustments are necessary.…”

Section: Discussionmentioning

confidence: 99%

“…Because ceftriaxone is 85 to 95% bound to plasma proteins (13,14), the lack of dialyzability of ceftriaxore was expected even though its V is relatively small.…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of its antibacterial activity (1,11)', ceftriaxone has the potential of providing an effective antibiotic regimen for the parenteral therapy of systemic bacterial infections in patients with reduced renal function. In recent studies (3,14) Sample analysis. Plasma, urine, and dialysate samples were analyzed for ceftriaxone by the reverse-phase, ionpairing high-pressure liquid chromatography procedure described previously (12).…”

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confidence: 99%

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Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment

Patel¹,

Sugihara²,

Weinfeld³

et al. 1984

Antimicrob Agents Chemother

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The effects of renal impairment on the pharmacokinetics of ceftriaxone in humans were examined after intravenous infusion of a 1-g dose over 15 min to 30 renally impaired patients. The study included 12 dialysis patients and 18 patients with severe, moderate, or mild renal impairment. Plasma and, where appropriate, urine and dialysate samples were collected at predetermined times and analyzed for ceftriaxone by highpressure liquid chromatography. The elimination half-life (group mean ranged from 11.7 to 17.3 h) and plasma clearance (group mean ranged from 529 to 705 ml/h) did not correlate linearly with creatinine clearance. The renal clearance and fraction of dose excreted unchanged in urine were related'linearly, however weakly, with creatinine clearance. Ceftriaxone was not, removed from plasma to a significant extent during hemodialysis. The half-life was prolonged twofold, the plasma clearance was lowered less than 50%, and the volume of distribution was relatively unchanged in renally impaired patients compared with young or elderly healthy subjects with normal renal function at an equivalent dose. Since these changes are moderate, adjustment in the dosage regimen of ceftriaxone for patients with impaired renal ftinction should not be necessary when ceftriaxone

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

“…Because ceftriaxone is 85 to 95% bound to plasma proteins (13,14), the lack of dialyzability of ceftriaxore was expected even though its V is relatively small.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment

Patel¹,

Sugihara²,

Weinfeld³

et al. 1984

Antimicrob Agents Chemother

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“…Reduced CLNRS with declining renal function have been reported for 1-lactam antibiotics such as cefsulodin (8), carumonam (11), cefixime (9), and ceftriaxone (16). The mechanism(s) responsible for this decline in CLNR has not been elucidated for f-lactam antibiotics that are primarily eliminated unchanged.…”

Section: Resultsmentioning

confidence: 96%

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with renal insufficiency

Kneer

Tam

Blouin

et al. 1989

Antimicrob Agents Chemother

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The pharmacokinetics of cefetamet after a short intravenous infusion of cefetamet (515 mg) and oral administration of 1,000 mg of cefetamet pivoxil were studied in 9 healthy subjects and in 38 patients with various degrees of renal impairment. The results showed that cefetamet elimination was dependent on renal function. After intravenous dosing, total body (CLs), renal (CLR), and nonrenal (CLNR) clearances were linearly related to creatinine clearance (CLCR; r = 0.95, 0.92, and 0.59, respectively). Elimination half-life (t112^) was prolonged from 2.46 ± 0.33 h in normal subjects to 29.1 13.9 h in patients with CLCR of <10 ml/min per 1.73 i2. Correspondingly, CLs and CLR decreased from 1.77 0.27 and 1.42 0.25 mI/mi per kg to 0.14 + 0.04 and 0.04 + 0.03 ml/min per kg, respectively. The volume of distribution at steady state (0.298 0.049 liter/kg) for cefetamet was not altered by renal insufficiency (P > 0.05). After oral administration, the elimination parameters, tl/2,, and CLR, were insignificantly different from the intravenous data (P > 0.05).Furthermore, the bioavailability (F) of cefetamet pivoxil (45 13%) was not altered by renal failure (P > 0.05). However, maximum concentration in plasma and the time to achieve this value were significantly increased (5.86 0.74 versus 14.8 6.14 ,ug/ml and 3.9 ± 1.1 versus 8.4 1.7 h, respectively; P < 0.05).Based on these observations, it is recommended that patients with CLCR of <10 ml/min per 1.73 m2 and between 10 and 39 ml/min per 1.73 m2 be given one-quarter of the normal daily dose either once or twice daily.Patients with CLCR between 40 and 80 ml/min per 1.73 m2 should receive one-half of the normal dose twice daily. For patients with CLCR of <10 ml/min per 1.73 m2, it would be recommended that they receive a normal standard dose as a loading dose on day 1 of treatment.Cefetamet pivoxil is the prodrug (pivaloyloxymethylester) of a new broad-spectrum cephalosporin antibiotic, cefetamet. This compound possesses a broad spectrum of antimicrobial activity against many aerobic gram-positive and gram-negative organisms (19). Previous pharmacokinetic studies in normal healthy volunteers revealed that the lowprotein-bound (22%) cefetamet is mainly eliminated by the kidneys via glomerular filtration (2, 12). This kinetic behavior is similar to that of other P-lactam antibiotics with low protein binding and high urinary recovery (e.g., carumonam [11], ceftizoxime [1,15], and ceftazidime [1,15]). Consequently, the pharmacokinetics of cefetamet are expected to be dependent on changes in renal function.The objectives of this study were to determine the pharmacokinetics of cefetamet and cefetamet pivoxil after intravenous and oral administration to patients with various degrees of impaired renal function, to compare these results with those obtained from healthy volunteers who have normal renal functions, and to determine dosage guidelines for patients with renal impairment. MATERIALS AND METHODSSubjects. Nine healthy volunteers (7 men and 2 women) and 38 patients (22 men and ...

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Lack of Probenecid Effect on Nonrenal Excretion of Ceftriaxone in Anephric Patients

Patel

Soni

Carbone

et al. 1990

The Journal of Clinical Pharma

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Probenecid has been shown to decrease renal and biliary excretion of organic acids. In a randomized crossover study, the effect of coadministered probenecid on nonrenal excretion of ceftriaxone was studied in six functionally anephric patients in whom ceftriaxone is eliminated exclusively by nonrenal or presumably by biliary excretion. Each patient received 0.5 g IV ceftriaxone without and with probenecid (0.5 g at 10 and 2 hours prior to ceftriaxone and 0.5 g q12h X 3 doses post ceftriaxone). Serial blood samples were collected over 48 hours and plasma analyzed for ceftriaxone by high performance liquid chromatography (HPLC). Pharmacokinetic analysis was based on a model-independent approach. Probenecid did not significantly affect the disposition of ceftriaxone in this study, thus suggesting that nonrenal excretion of ceftriaxone is not inhibited by probenecid.

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Single-dose ceftriaxone kinetics in functionally anephric patients

Cited by 39 publications

References 0 publications

Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment

Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with renal insufficiency

Lack of Probenecid Effect on Nonrenal Excretion of Ceftriaxone in Anephric Patients

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