Pharmacokinetics of Once-Daily Ip Gentamicin in Capd Patients

1996 ◽  
Vol 16 (4) ◽  
pp. 379-384 ◽  
Author(s):  
Chai Luan Low ◽  
George R. Bailie ◽  
Anne Evans ◽  
George Eisele ◽  
Richard A. Venezia
Keyword(s):  
Renal Function ◽  
Open Study ◽  
Residual Renal Function ◽  
Volume Of Distribution ◽  
Peritoneal Membrane ◽  
Time Data ◽  
Once Daily ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean

Objective This study aimed to investigate the pharmacokinetic characteristics of once-daily intraperitoneal (IP) gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients. Design Prospective, nonrandomized, open study. Setting CAPD outpatient clinic in a teaching hospital. Patients Ten volunteer CAPD patients without peritonitis. Interventions Each patient received a single IP dose of 0.6 mg/kg of gentamicin. Blood and dialysate samples were collected at 0,0.5,1, 2, 3,6 (end of first dwell), and 24 hours after the administration of IP gentamicin. Any urine produced over the 24hour study period was also collected. The dialysate concentration/time data were fitted to a monoexponential curve for all patients. Results The bioavailability was 56±11% over a six hour dwell. The mean serum elimination half-life (t1/2) was 35.8 hours. The volume of distribution was 0.23±0.08 L/kg. Equilibration of gentamicin across the peritoneal membrane was rapid, with a t½ equilibration of 4.5 hours. The peritoneal clearance was 5.74±1.5 mL/min. Patients with residual renal function had significantly higher systemic gentamicin clearances (7.36±1.46 mL/min) than those of anuric patients (4.76±1.08 mL/min, p < 0.024). Conclusion Currently recommended doses of oncedaily IP gentamicin for the treatment of peritonitis may not produce the desired therapeutic serum and dialysate concentrations over 24 hours for effective treatment of peritonitis.

scholarly journals Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

Pharmacokinetics of Intravenous and Intraperitoneal Cefotaxime in Patients Undergoing CAPD

1985 ◽  
Vol 5 (1) ◽  
pp. 33-35 ◽  
Author(s):  
Karel Matousovic ◽  
Josef Moravek Stefan ◽  
Vitko Vladimir Prat ◽  
Milena Horcickova
Keyword(s):  
Renal Function ◽  
Renal Insufficiency ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Peritoneal Membrane ◽  
Severe Renal Insufficiency ◽  
Elimination Half ◽  
Stage Renal Disease ◽  
End Stage ◽  
Dialysis Solutions

We investigated the pharmacokinetics of non-metabolized cefotaxime in 10 patients undergoing CAPD. The elimination half-life after IV administration of I g cefotaxime was 3.1 ± 1.3 hr, i.e. two to three times longer than in individuals with normal renal function but similar to patients with severe renal insufficiency. An average of 2.18% of the dose was recovered in the effluent. The halflife of I g cefotaxime administered in the dialysis solutions was 1.4 ± 0.8 hr. This difference between the half-lives after intraperitoneal and intravenous administration indicates a faster transport through the peritoneal membrane. Intraperitoneally administered cefotaxime -250 mg four times daily, was effective in the treatment of peritonitis in three CAPD patients. Since its introduction in 1976, CAPD has become an effective therapy for end-stage renal disease. The most serious complication is peritonitis and effective treatment is essential. Cefotaxime, a new broad-spectrurn cephalosporin, is active against most gramnegative and gram-positive organisms. It possesses no nephrotoxicity and may be useful in the treatment of peritonitis and other infections in patients on CAPD. This study was done to evaluate the pharmacokinetics of cefotaxime administered intravenously and intraperitoneally during CAPD.

Impact of Peritoneal Membrane Function on Long Term Clinical Outcome in Peritoneal Dialysis Patients

1999 ◽  
Vol 19 (2_suppl) ◽  
pp. 91-94 ◽  
Author(s):  
Simon J. Davies ◽  
Louise Phillips ◽  
Anne M. Griffiths ◽  
Lesley H. Russell ◽  
Patrick F. Naish ◽  
...  
Keyword(s):  
Renal Function ◽  
Solute Transport ◽  
Residual Renal Function ◽  
Clinical Implications ◽  
Water Removal ◽  
Peritoneal Membrane ◽  
Dialysis Patients ◽  
Membrane Function

It is increasingly clear that peritoneal membrane transport status has clinical implications. The role of the peritoneum in dialysis delivery becomes para mount once residual renal function is lost, particularly as the membrane characteristics may change for the worse with time on treatment. These findings have several important implications: Clinicians need to take solute transport character istics into account as they assess their patients. Adverse effects of high solute transport include reduced ultrafiltration, solute removal (in particular, sodium), and increased peritoneal protein losses. A need exists to replace lost residual renal function, not just with enhanced solute removal, but also with adequate salt and water removal. The interpretation of urea and creatinine clear ances in anuric PD patients needs further consideration and validation. Hypoalbuminemia in PD patients will result from the combined effects of high protein losses, over hydration, comorbidity, and malnutrition.

Association of Carnitine Deficiency in Indian Continuous Ambulatory Peritoneal Dialysis Patients with Anemia, Erythropoietin Use, Residual Renal Function, and Diabetes Mellitus

2007 ◽  
Vol 27 (2_suppl) ◽  
pp. 235-238
Author(s):  
S. Ramalakshmi ◽  
Bjoe Baben ◽  
Ben S. Ashok ◽  
V. Jayanthi ◽  
Nancy Leslie ◽  
...  
Keyword(s):  
Renal Function ◽  
Peritoneal Dialysis ◽  
Residual Renal Function ◽  
Carnitine Deficiency ◽  
Free Carnitine ◽  
Dialysis Patients ◽  
Carnitine Level ◽  
Daily Urine ◽  
The Mean ◽  
Daily Urine Output

♦ In the present study, we aimed to determine levels of free carnitine in hemodialysis (HD) and peritoneal dialysis (PD) patients in India and to correlate carnitine deficiency with various clinical parameters. ♦ Patients on HD and PD at two tertiary care centers were selected for the study. Baseline data were obtained, and a free carnitine analysis was performed. Carnitine deficiency was defined as a free carnitine level of less than 40 μmol/L. ♦ The total number of study patients was 96 (77 on HD, 19 on PD). In the PD group, the mean age was 56 years, with 26.3% of the patients being vegan, 47.4% having diabetes, and 57.9% having a daily urine output of <500 mL. The mean carnitine level in that group was 38.9 μmol/L, and 68.4% of the patients had a carnitine deficiency. A Pearson correlation test failed to show any association of carnitine level with parameters such as anemia, use of erythropoietin, non-vegetarian diet, diabetes, and hypertension. In the HD group, the mean age was 45 years, with 22% of the patients being vegan, 23% having diabetes, and 45.5% having a daily urine output of <500 mL. The mean carnitine level in the group was 38.2 μmol/L, and 64.3% of the patients had a carnitine deficiency. Residual renal function and duration of dialysis were different in HD patients with and without carnitine deficiency. Carnitine levels in the HD group correlated positively and statistically significantly with the presence of diabetes and hypertension. ♦ Conclusion This study is the first demonstration that Indian dialysis patients have carnitine deficiency.

Risk Factors for Early Mortality in U.S. Peritoneal Dialysis Patients: Impact of Residual Renal Function

2002 ◽  
Vol 22 (3) ◽  
pp. 371-379 ◽  
Author(s):  
◽  
Michael V. Rocco ◽  
Diane L. Frankenfield ◽  
Barbara Prowant ◽  
Pamela Frederick ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Renal Function ◽  
Peritoneal Dialysis ◽  
Serum Albumin ◽  
Creatinine Clearance ◽  
Residual Renal Function ◽  
Chronic Peritoneal Dialysis ◽  
Dialysis Patients ◽  
The Mean

Background Potential risk factors for 1-year mortality, including the peritoneal component of dialysis dose, residual renal function, demographic data, hematocrit, serum albumin, dialysate-to-plasma creatinine ratio, and blood pressure, were examined in a national cohort of peritoneal dialysis patients randomly selected for the Centers for Medicare and Medicaid Services End-Stage Renal Disease (ESRD) Core Indicators Project. Methods The study involved retrospective analysis of a cohort of 1219 patients receiving chronic peritoneal dialysis who were alive on December 31, 1996. Results During the 1-year follow-up period, 275 patients were censored and 200 non censored patients died. Among the 763 patients who had at least one calculable adequacy measure, the mean [± standard deviation (SD)] weekly Kt/V urea was 2.16 ± 0.61 and the mean weekly creatinine clearance was 66.1 ± 24.4 L/1.73 m2. Excluding the 365 patients who were anuric, the mean (±SD) urinary weekly Kt/V urea was 0.64 ± 0.52 (median: 0.51) and the mean (±SD) urinary weekly creatinine clearance was 31.0 ± 23.3 L/1.73 m2 (median: 26.3 L/1.73 m2). By Cox proportional hazard modeling, lower quartiles of renal Kt/V urea were predictive of 1-year mortality; lower quartiles of renal creatinine clearance were of borderline significance for predicting 1-year mortality. The dialysate component of neither the weekly creatinine clearance nor the weekly Kt/V urea were predictive of 1-year mortality. Other predictors of 1-year mortality ( p < 0.01) included lower serum albumin level, older age, and the presence of diabetes mellitus as the cause of ESRD, and, for the creatinine clearance model only, lower diastolic blood pressure. Conclusion Residual renal function is an important predictor of 1-year mortality in chronic peritoneal dialysis patients.

scholarly journals Multiple-Dose Pharmacokinetics and Safety of the New Antifungal Triazole BAL4815 after Intravenous Infusion and Oral Administration of Its Prodrug, BAL8557, in Healthy Volunteers

2006 ◽  
Vol 50 (1) ◽  
pp. 286-293 ◽  
Author(s):  
Anne Schmitt-Hoffmann ◽  
Brigitte Roos ◽  
Jürgen Maares ◽  
Markus Heep ◽  
Jochen Spickerman ◽  
...  
Keyword(s):  
Active Drug ◽  
Volume Of Distribution ◽  
Water Soluble ◽  
Time Curve ◽  
Once Daily ◽  
Routes Of Administration ◽  
Elimination Half ◽  
Constant Rate ◽  
Phase 2 Study ◽  
Multiple Dose Pharmacokinetics

ABSTRACT BAL8557 is the water-soluble prodrug of BAL4815, a new broad-spectrum antifungal. Healthy male subjects were randomly assigned to four treatment cohorts to receive multiple oral doses or multiple 1-h constant-rate intravenous infusions of BAL8557. Loading doses of BAL8557 were equivalent to 100 mg (followed by once-daily maintenance doses of 50 mg) or 200 mg (followed by once-daily maintenance doses of 100 mg) of BAL4815. In each cohort, six subjects received active drug and two subjects received the placebo. Study duration was 21 days (oral) and 14 days (intravenous). All adverse events reported were mild or moderate, except one severe rhinitis event which was not related to trial medication. After both routes of administration, maximum drug concentration observed in plasma (C max) and area under the concentration-time curve (AUC) values of BAL4815 increased proportionally to the administered dose. AUC values reflected a fourfold to fivefold accumulation of active drug in plasma during once-daily dosing, which is in line with the long elimination half-life of BAL4815 determined after the last administration (mean, 84.5 to 117 h). At steady state, the volume of distribution was large and amounted to 308 to 542 liters. Systemic clearance reached only 2.4 to 4.1 liter/h. At the levels obtained in the present study, C max values of 2.56 and 2.55 μg/ml after oral and intravenous administrations, respectively, there was no indication of CYP3A4 induction or inhibition (as revealed by the urinary 6-β-hydroxycortisol/cortisol test). Based on AUC values after oral and intravenous administration, an excellent oral bioavailability can be predicted for BAL4815. Once-daily oral dosing of 50- or 100-mg equivalents of BAL8557 were recently demonstrated to be efficacious in a phase 2 study conducted with patients with esophageal candidiasis. These doses (preceded by adequate loading dose[s]) will be further explored in the treatment of systemic mycoses.

Elimination of Iomeprol in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

1999 ◽  
Vol 19 (4) ◽  
pp. 380-385 ◽  
Author(s):  
Masako Iwamoto ◽  
Kinya Hiroshige ◽  
Takeshi Suda ◽  
Takayuki Ohta ◽  
Akira Ohtani ◽  
...  
Keyword(s):  
Renal Function ◽  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Elimination Rate ◽  
Iodine Concentration ◽  
Residual Renal Function ◽  
University Hospitals ◽  
Before And After ◽  
Peritoneal Permeability ◽  
The Mean

Objective To examine the elimination of iomeprol, its safety in clinical use, and its peritoneal permeability in continuous ambulatory peritoneal dialysis (CAPD) patients with variable degrees of residual renal function (RRF). Design A nonrandomized comparison study. Setting Hospitalized patients in CAPD unit of Chikuho and University Hospitals. Participants Fourteen patients treated by CAPD and 6 by hemodialysis (HD). Interventions Total dialysate, blood, and 24-hour urine collections were obtained for 4 consecutive days after the administration of iomeprol. A peritoneal equilibration test was performed just before and after the administration of iomeprol. Measurements Iomeprol (iodine) concentration was measured. Residual renal function was estimated as the mean of renal creatinine and urea clearances. Dialysate-to-plasma ratios (D/P) of creatinine and iomeprol were also determined. Results In all CAPD patients, plasma iomeprol clearance was markedly slow, with a biological half-life ( T1/2) of over 32 hours. However, no patients suffered from any adverse effects, and over 80% of plasma iomeprol was eliminated during the 4-hour HD. The plasma iomeprol elimination rate was significantly higher from 4 hours after the iomeprol administration in CAPD patients with RRF [mean estimated creatinine clearance (CCr) 3.8 mL/min, n = 7] compared to the remaining patients (mean estimated CCr 0.6 mL/min, n = 7); however, T1/2 in patients with RRF was over 24 hours. D/P creatinine was significantly correlated with D/P iomeprol, and peritoneal iomeprol permeability may depend on an individual's peritoneal solute transport properties. Conclusions A prolonged elimination rate of iomeprol was documented in our CAPD patients both with and without RRF. A HD procedure or intensive peritoneal dialysis just after the use of iomeprol may be advisable to promptly remove circulating iomeprol.

Individualized Once-Daily Dosing of Intravenous Busulfan: A Pharmacokinetic Study in Patients Undergoing Conditioning for Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 98-98 ◽  
Author(s):  
Shabal B. Kangarloo ◽  
Farrukh Naveed ◽  
Borje S. Andersson ◽  
Diana Quinlan ◽  
James A. Russell
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Correction Factor ◽  
Half Life ◽  
Therapeutic Dose ◽  
Test Dose ◽  
High Dose ◽  
Once Daily ◽  
Concentration Time ◽  
The Mean

Abstract Background: Busulfan (Bu) given in myeloablative doses is a frequent component of preparative regimens for hematopoietic stem cell transplantation. Variations in the area under the concentration/time curve (AUC) for oral Bu may result in over/under dosing, which may increase the risk of toxicity or reduce efficacy. The availability of an IV formulation of busulfan reduces this by eliminating variability in absorption but inter-patient differences in metabolism remain. A pharmacokinetically guided test dose strategy before the high dose Bu may be used to achieve a specific target AUC. Purpose: To establish a reliable model to predict a therapeutic dose of IV Bu from a small test dose in order to improve inter-patient variability in AUC. Methods: Pharmacokinetic (PK) analysis was performed on 35 paired patient samples, comparing a limited sampling test dose to the therapeutic high dose. For the test dose, an AimPlus infusion pump was used to administer 12 mg of IV Bu over a 20-minute infusion on day −6. High dose Bu was given at a dose of 3.2mg/kg daily over 4 hours on days −5 to −2. The test dose PK parameters were compared to the high dose IV Bu PK parameters on day −3. Busulfan concentrations in plasma were determined by UV-HPLC. All concentration-time plasma Bu data were analyzed by non-compartmental analysis using WinNonlin Version 4.1 software (Pharsight Corporation, Mountain View, CA, USA). Results: The mean (CV%) PK parameters for the 12 mg test dose patients were as follows: Cmax, 0.36 ug/mL (30.4%); clearance (CL), 16.3 L/hr (21.4%); volume of distribution Vd, 57.4 L (26.1%); elimination half-life, 2.4 hr (16.1%); and AUC, 199 μM.min (23.6%). The mean (CV%) Cmax, CL, Vd, half-life, and AUC for the once daily high dose were 3.95 ug/mL (22%), 11.7 L/hr (25.4%), 46.3 L (25.3%), 2.8 hr (15.6%), and 5190 μM.min (22.7%) respectively. The range of AUC for the high dose was 2832 to 7354 μM.min. The ratio of the high dose over the test dose required a correction factor “k” of 1.45 to be equivalent to the ratio of the AUC high dose over the AUC test dose. Conclusion: Dosing based on patient weight results in 2–3 fold variability of AUC. The fact that a correction factor based on the test dose is needed is most likely due to the statistically significantly higher CL of busulfan during the test dose as compared to the high dose CL. This raises questions concerning the proposed linear kinetics of IV busulfan. However using the above correction factor and given a target therapeutic AUC, it is possible to individualize the therapeutic dose for IV busulfan based on this test dose strategy.

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