<i>N</i>‐Acetylprocainamide pharmacokinetics in functionally anephric patients before and after perturbation by hemodialysis

Stec, Grzegorz; Atkinson, Arthur J.; Nevin, Mary Jane; Thénot, Jean Paul; Ruo, Tsuen Ih; Gibson, Thomas; Ivanovich, Peter; Greco, Francesco

doi:10.1002/cpt1979265618

Cited by 55 publications

(22 citation statements)

References 10 publications

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“…Ampicillin rebound was more evident than sulbactam rebound. This rebound phenomenon has been attributed to blood flow alterations encountered as a consequence of hemodialysis (12). With the restoration of normal hemodynamic conditions at the completion of the dialysis period, a release of drugs from the sequestration sites forces re-equilibrium to occur (16 …”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis

Blum

Kohli

Harrison

et al. 1989

Antimicrob Agents Chemother

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The single-dose pharmacokinetics of intravenously administered ampicillin (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of creatinine clearance (CLCR). Six normal subjects (CLCR, >60 ml/min), six patients with mild renal failure (CLCR, 31 to 60 ml/min), four patients with severe renal failure (CLCR, 7 to 30 ml/min), and four patients requiring maintenance hemodialysis (CLCR, <7 ml/min) were studied. The terminal half-lives for ampicillin and sulbactam more than doubled in patients with severe renal failure compared with subjects with normal renal function and mild renal insufficiency. CLCR significantly correlated with ampicillin (r = 0.88) and sulbactam (r = 0.54) total body clearance. Mean steady-state volume of distribution and nonrenal clearance for ampicillin and sulbactam were not affected by renal function. Hemodialysis approximately doubled the ampicillin and sulbactam total body clearance. Mean totals of 34.8 4.0% of the ampicillin dose and 44.7 + 3.2% of the sulbactam dose were removed during a 4-h hemodialysis treatment. A slight rebound in concentrations in serum after hemodialysis was observed for both drugs in all four subjects. In hemodialysis patients, the ampicillin half-life was 17.4 8.0 h and the sulbactam half-life was 13.4 + 7.4 h. The ampicillin and sulbactam half-lives were appreciably altered during the hemodialysis period (means of 2.2 and 2.3 h, respectively). The nearly parallel decrease in total body clearance, with volume of distribution and nonrenal clearance remaining relatively constant, suggests that the same ratio of ampicillin to sulbactam is appropriate regardless of renal function. An adjustment of the ampicillin (2.0 g) and sulbactam (1.0 g) dose to twice daily would be appropriate in patients with a CLCR between 7 and 30 ml/min. Doses should be given every 24 h for those undergoing maintenance hemodialysis. On hemodialysis days, doses should be given after hemodialysis.Ampicillin-sulbactam is a broad-spectrum, bactericidal, P-lactamase-resistant antimicrobial combination with potent activity against Haemophilus influenzae, Branhamella catarrhalis, Neisseria species, and most gram-positive and anaerobic pathogens (3,9,10,13). Coadministration of sulbactam appears to have very little effect on the pharmacokinetics of ampicillin, suggesting that coadministration of the sulbactam will not affect the usual dosing regimens for ampicillin (5). The pharmacokinetics of sulbactam are very similar to those of ampicillin in subjects with normal renal function (2,4,5,11,14). The purposes of this study were to evaluate the pharmacokinetics of ampicillin-sulbactam in subjects with various degrees of renal function to evolve dosage guidelines and to determine the effect of hemodialysis on the clearances of ampicillin and sulbactam.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis

Blum

Kohli

Harrison

et al. 1989

Antimicrob Agents Chemother

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“…At the end of the incubation period, a l-mm3 piece of tissue from the tail of each pancreas was minced and placed in a perfusion apparatus (7). After 30 min, the glucose concentration of the perfusate was increased to 300 mg% from an initial value of 30 mg%.…”

Section: Methodsmentioning

confidence: 99%

Charcoal Hemoperfusion for Treatment of Ethchlorvynol Overdose

1983

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Charcoal hemoperfusion is commonly employed to treat overdose of a number of drugs. There are varying reports of its efficacy in the treatment of ethchlorvynol overdose. Herein is reported a case of ethchlorvynol overdose successfully treated with charcoal hemoperfusion within 5 h of ingestion of 12.5 g of the drug. The patient was deeply comatose at that time but recovered consciousness at the end of 4 h of hemoperfusion. Ethchlorvynol clearance over the charcoal varied from 118 to 147 ml/min. There were no bleeding complications. Prompt charcoal hemoperfusion may be an effective mode of treatment in cases of ethchlorvynol intoxication.

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“…This parameter was fixed based on reported values in the literature of NAPA disposition in functionally anepheric patients on hemodialysis (approximately 1.5 L/kg). 9 Based on this patient’s weight (70 kg), (V c ) N was fixed to 100 L and all other parameters were successfully estimated. The estimated PK parameters from the final model are displayed in Table1.…”

Section: Case Reportmentioning

confidence: 99%

“…7–9 Several studies have evaluated the efficiency of different renal replacement therapies in removal of both compounds in patients with diminished kidney function. 10–12 However, elimination in patients with CKD who are undergoing continuous renal replacement therapy (CRRT) has not been evaluated.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Modeling and Simulation of Procainamide and N-Acetylprocainamide in a Patient Receiving Continuous Renal Replacement Therapy: A Novel Approach to Guide Renal Dose Adjustments

Mohamed

Abdelhady

Spencer

et al. 2013

American Journal of Kidney Diseases

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Procainamide and its major metabolite, N-acetyl procainamide (NAPA), prolong the QTc interval and can promote potentially fatal ventricular arrhythmias. Excretion of procainamide and NAPA is reduced in patients with chronic kidney disease (CKD) resulting in drug accumulation and toxicity. The elimination of procainamide or NAPA in patients undergoing continuous renal replacement therapy (CRRT) has not been evaluated increasing the risk for subtherapeutic or toxic dosing regimens. This case report describes a patient undergoing CRRT who was administered procainamide for recurring ventricular tachycardia (VT) over approximately a 36 hour period. The patient required increased vasopressor therapy and developed QTc prolongation during procainamide administration. The VT resided following pacemaker adjustments, procainamide administration, and multiple direct current cardioversion attempts. Procainamide and NAPA concentrations were determined over a 120 hour period as part of routine clinical care and a pharmacokinetic (PK) model was developed using NONMEM. The developed PK model was used to simulate several procainamide dosing regimens to optimize therapy during CRRT. Based on the model-based simulations, a 50% reduction in the procainamide maintenance dose (2 mg/min) in CKD patients on CRRT can achieve therapeutic plasma procainamide and combined procainamide/NAPA concentrations.

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N‐Acetylprocainamide pharmacokinetics in functionally anephric patients before and after perturbation by hemodialysis

Cited by 55 publications

References 10 publications

Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis

Pharmacokinetics of ampicillin (2.0 grams) and sulbactam (1.0 gram) coadministered to subjects with normal and abnormal renal function and with end-stage renal disease on hemodialysis

Charcoal Hemoperfusion for Treatment of Ethchlorvynol Overdose

Pharmacokinetic Modeling and Simulation of Procainamide and N-Acetylprocainamide in a Patient Receiving Continuous Renal Replacement Therapy: A Novel Approach to Guide Renal Dose Adjustments

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