Pharmacokinetics of Creatinine in Man and Its Implications in the Monitoring of Renal Function and in Dosage Regimen Modifications in Patients with Renal Insufficiency

Chiou, Win L.; Hsu, Ho-Chi

doi:10.1002/j.1552-4604.1975.tb02364.x

Cited by 79 publications

(53 citation statements)

References 24 publications

(1 reference statement)

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“…Daily serum creatinine values were obtained throughout the duration of ABCD treatment for each patient. The normalized (to 70 kg) CL CR s were predicted daily by an equation that allowed for changing serum creatinine (4,36). The median weekly CL CR s during the first (CL CR1 ) and last (CL CR2 ) weeks of ABCD therapy were determined and compared statistically by the Wilcoxon signed rank test.…”

Section: Patient Selectionmentioning

confidence: 99%

Population pharmacokinetics and renal function-sparing effects of amphotericin B colloidal dispersion in patients receiving bone marrow transplants

Amantea¹,

Bowden²,

Forrest³

et al. 1995

Antimicrob Agents Chemother

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The purpose of this study was to evaluate the pharmacokinetics of amphotericin B colloidal dispersion and its effect on creatinine clearance in bone marrow transplant patients with systemic fungal infections. Seventyfive patients (42 females and 33 males) with a median age of 34.5 years and a median weight of 70.0 kg were enrolled in the study. Patients received 1 of 15 dose levels (range, 0.5 to 8.0 mg/kg of body weight) daily for a mean duration of 28 days and a mean cumulative dose amount of 8 g. Plasma samples for amphotericin B determination (median number, 4; range, 2 to 30) and daily serum creatinine values were obtained for each patient. Iterative two-stage analysis, one of several approaches to population pharmacokinetic and pharmacodynamic modelling, was employed for the pharmacokinetic analysis. The plasma data were available for 51 of 75 patients and were best described by a two-compartment model. Both plasma clearance and volume of distribution increased with escalating doses; the overall average terminal elimination half-life was 29 h. Of the covariates studied, only body weight and dose size were significant. Serum creatinine values over the duration of therapy were available for 59 of 75 patients. Overall, there was no net change in renal function over the duration of therapy; 12 patients had >30% increases in creatinine clearance, whereas 13 had >30% decreases. No measure of amphotericin B colloidal dispersion exposure, demographic values, or concomitant treatment with other medications was related to changes in the creatinine clearance.Patients undergoing bone marrow transplant procedures receive a plethora of immunosuppressive agents. These patients are vulnerable to infections with a number of opportunistic organisms, including fungi. In a recent review of over 1,500 patients undergoing bone marrow transplants, the incidence of invasive candidiasis was 11% and that of invasive aspergillosis was 4.5%, with mortalities of 73 and 84%, respectively (22).Amphotericin B (AmB), a polyene antibiotic that is available as a deoxycholate micellar dispersion (DAmB), has been the mainstay of systemic antifungal therapy for almost 4 decades. Its antifungal activity is due to its affinity for sterols (ergosterols) found in the membranes of fungal cells. However, its undesirable binding to host cell sterols is believed to account for its various toxicities, which include nausea, vomiting, chills, fever, anemia, and thrombophlebitis (14,21,27). The primary dose-limiting toxicity of AmB is nephrotoxicity, which occurs in up to 80% of patients receiving cumulative doses of 4 to 5 g. Consequently, the cumulative amount of AmB that can be administered to patients and the duration of treatment are limited (12, 15). The potential for nephrotoxicity poses a therapeutic challenge for bone marrow transplant recipients, for whom long-term therapy with DAmB for the treatment of systemic suspected or documented fungal disease is generally required. Furthermore, many of these patients are receiving other nephrotoxic drugs...

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Section: Patient Selectionmentioning

confidence: 99%

Population pharmacokinetics and renal function-sparing effects of amphotericin B colloidal dispersion in patients receiving bone marrow transplants

Amantea¹,

Bowden²,

Forrest³

et al. 1995

Antimicrob Agents Chemother

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“…The steady state, however, may not be reached for several days after an episode of AKI. 3,4 We hypothesized that the arbitrary percentage change thresholds incorporated in the RIFLE criteria 1 "R" and "I" and the second stage of the AKIN criteria 2 will significantly delay the diagnosis of AKI in patients with CKD, because the level of baseline kidney function may influence the kinetics of creatinine rise after an acute injurious event to the kidney. CKD, which may affect Ͼ10% of the US population, 5 is a major risk factor for AKI and is present in Ͼ30% of patients who develop severe AKI.…”

mentioning

confidence: 99%

Creatinine Kinetics and the Definition of Acute Kidney Injury

Waikar

Bonventre²

2009

Journal of the American Society of Nephrology

551

401

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Acute kidney injury (AKI) is a common and devastating medical condition, but no widely accepted definition exists. A recent classification system by the Acute Dialysis Quality Initiative (RIFLE) defines AKI largely by percentage increases in serum creatinine (SCr) over baseline. The Acute Kidney Injury Network defines the first stage by either an absolute or a percentage increase in SCr. To examine the implications of various definitions, we solved differential equations on the basis of mass balance principles. We simulated creatinine kinetics after AKI in the setting of normal baseline kidney function and stages 2, 3, and 4 chronic kidney disease (CKD). The percentage changes in SCr after severe AKI are highly dependent on baseline kidney function. Twenty-four hours after a 90% reduction in creatinine clearance, the rise in SCr was 246% with normal baseline kidney function, 174% in stage 2 CKD, 92% in stage 3 CKD, and only 47% in stage 4 CKD. By contrast, the absolute increase was nearly identical (1.8 to 2.0 mg/dl) across the spectrum of baseline kidney function. Time to reach a 50% increase in SCr was directly related to baseline kidney function: From 4 h (normal baseline) up to 27 h for stage 4 CKD. By contrast, the time to reach a 0.5-mg/dl increase in SCr was virtually identical after moderate to severe AKI (Ͼ50% reduction in creatinine clearance). We propose an alternative definition of AKI that incorporates absolute changes in SCr over a 24-to 48-h time period.

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“…and equation 3 may be solved numerically, or, if we assume of G, V,o rk r are not varying, may be integrated to give the concentration as a function of time (Chiou & Hsu (1975);Chow (1985)):…”

Section: Fig 2 One Compartment Pharmacokinetics Modelmentioning

confidence: 99%

“…However, serum creatinine increases slowly in response to a single step alteration in GFR. Serum creatinine has a half-life of approximately 4 hours when GFR is normal and 77 hours when GFR is reduced to 5% (Chiou & Hsu (1975); see section 3.1). As 3 to 5 half-lives are required after any change in GFR to obtain a new steady-state estimate, a reliable GFR based on the serum creatinine will require at least 12 hrs after even a minimal change in GFR.…”

Section: Introductionmentioning

confidence: 99%