Pharmacokinetic Studies of Propoxyphene IV: Effect of Renal Failure on Systemic Clearance in Rats

1980 ◽  
Vol 69 (3) ◽  
pp. 363-364 ◽  
Author(s):  
Stephen M. Roberts ◽  
Gerhard Levy
Keyword(s):  
Renal Failure ◽  
Pharmacokinetic Studies ◽  
Systemic Clearance

A phase I clinical and pharmacokinetic study of carboplatin and autologous bone marrow support.

1989 ◽  
Vol 7 (5) ◽  
pp. 651-661 ◽  
Author(s):  
T C Shea ◽  
M Flaherty ◽  
A Elias ◽  
J P Eder ◽  
K Antman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Autologous Bone Marrow ◽  
Recurrent Ovarian Cancer ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Studies ◽  
Systemic Clearance ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Autologous Bone

A series of 33 patients were treated with a four-day continuous infusion of carboplatin in a phase I study to determine the maximum-tolerated dose (MTD) of this agent when used with autologous bone marrow reinfusion. Doses were escalated from 375 to 2,400 mg/m2; autologous bone marrow reinfusion was added to the regimen at doses of 1,600 mg/m2 and above. The MTD was determined to be 2,000 mg/m2. Dose-limiting toxicity consisting of reversible hepatotoxicity, renal dysfunction, and moderate to severe ototoxicity was observed with a dose of 2,400 mg/m2. There were ten responses in 31 heavily pretreated patients, including six responses in 11 patients with recurrent ovarian cancer. Pharmacokinetic studies revealed a systemic clearance (Clss) of 4.5 L/m2/h. This value is consistent with clearances reported for carboplatin administered at lower doses and by different schedules. No evidence for saturation of systemic clearance at higher doses was observed. Carboplatin appears to be an active drug that can undergo considerable dose escalation when used in conjunction with autologous bone marrow support.

Pharmacokinetic, oral bioavailability, and safety study of fluorouracil in patients treated with 776C85, an inactivator of dihydropyrimidine dehydrogenase.

1996 ◽  
Vol 14 (12) ◽  
pp. 3085-3096 ◽  
Author(s):  
S D Baker ◽  
S P Khor ◽  
A A Adjei ◽  
M Doucette ◽  
T Spector ◽  
...  
Keyword(s):  
Dihydropyrimidine Dehydrogenase ◽  
Kinetic Studies ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Oral Solution ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Studies ◽  
Systemic Clearance ◽  
Calculated Creatinine Clearance ◽  
Apparent Volume Of Distribution

PURPOSE To study the absolute bioavailability and pharmacokinetics of an oral solution of fluorouracil (5-FU) in patients treated with 776C85, an oral inactivator of dihydropyrimidine dehydrogenase (DPD), and to evaluate the feasibility of administering oral 5-FU and 776C85 on a multiple-daily dosing schedule. PATIENTS AND METHODS Twelve patients with refractory solid tumors were enrolled onto this three-period study. In periods 1 and 2, patients were randomly assigned to treatment with 5-FU 10 mg/m2 on day 2 given by either the oral or intravenous (IV) route with oral 776C85 3.7 mg/m2/d on days 1 and 2. In period 3, patients received escalating doses of 5-FU (10 to 25 mg/ m2/d) orally for 5 days (days 2 to 6) with 776C85 3.7 mg/m2/d orally (days 1 to 7) every 4 weeks. Pharmaco-kinetic studies were performed in periods 1 and 2, and after the fifth oral dose of 5-FU in period 3. RESULTS Twelve patients completed the bioavailability and pharmacokinetic studies. Following oral 5-FU 10 mg/m2, the bioavailability was 122% +/- 40% (mean +/- SD), the terminal half-life (t1/2 beta) was 4.5 +/- 1.6 hours, the apparent volume of distribution (V beta) was 21.4 +/- 5.9 L/ m2, and the systemic clearance (Clsys) was 57.6 +/- 16.4 mL/min/m2. A correlation was observed between oral 5-FU systemic clearance and calculated creatinine clearance (r = .74; P = .009). Multiple-daily dosing did not appear to affect the pharmacokinetics of oral 5-FU. Neutropenia was the principal toxicity of oral 5-FU and 776C85, precluding escalation of oral 5-FU to doses greater than 25 mg/m2/d for 5 days every 4 weeks with 776C85. CONCLUSION The oral DPD inactivator 776C85 enables oral administration of 5-FU and may alter conventional 5-FU administration practices.

scholarly journals Nonattenuated Polymyxin B Used for the Treatment of Extreme-Drug ResistantAcinetobacter baumannii-Related Infections in Patients with Preexisting End Stage Renal Failure

2014 ◽  
Vol 2014 ◽  
pp. 1-3
Author(s):  
Yvonne Peijun Zhou ◽  
Nathalie Grace Sy Chua ◽  
Maciej Piotr Chlebicki ◽  
Winnie Hui Ling Lee ◽  
Andrea Lay Hoon Kwa
Keyword(s):  
Renal Failure ◽  
Adverse Events ◽  
Polymyxin B ◽  
Resistant Organism ◽  
Pharmacokinetic Studies ◽  
Drug Resistant ◽  
End Stage Renal Failure ◽  
End Stage

Recent pharmacokinetic studies have suggested that nonrenal clearance predominates the elimination of polymyxin B. We present 2 patients with preexisting end stage renal failure, who were given nonattenuated doses of polymyxin B for the treatment of extreme-drug resistant organism. No evidence of adverse events occurred and microbiological clearance was documented.

Pyrazinamide and Rifampicin Regimens for Patients on Maintenance Dialysis

1988 ◽  
Vol 11 (3) ◽  
pp. 181-185 ◽  
Author(s):  
J. Woo ◽  
A. Leung ◽  
K. Chan ◽  
K.N. Lai ◽  
R. Teoh
Keyword(s):  
Renal Failure ◽  
Peritoneal Dialysis ◽  
Plasma Concentrations ◽  
Pharmacokinetic Studies ◽  
Bactericidal Action ◽  
Dialysis Treatment ◽  
End Stage Renal Failure ◽  
Maintenance Dialysis ◽  
End Stage ◽  
Higher Doses

We measured pyrazinamide and rifampicin plasma concentrations in five patients with pulmonary tuberculosis and end stage renal failure treated by haemodialysis or continuous ambulatory peritoneal dialysis. Using conventional daily doses of oral pyrazinamide and rifampicin, we found that the drugs were removed efficiently by both dialysis methods, so that plasma levels were sub-optimal for maximal bactericidal action. These findings suggest that in patients with tuberculosis on maintenance dialysis, treatment should be either with higher doses of these two drugs, or with additional replacement doses given after each dialysis. Further detailed pharmacokinetic studies on larger numbers of patients are indicated.

scholarly journals Pharmacokinetic Studies of L-DOPS (L-threo-3,4-Dihydroxyphenylserine) in Renal Failure Rats.

1994 ◽  
Vol 9 (6) ◽  
pp. 809-819
Author(s):  
Fumiaki SHONO ◽  
Masaki ITO ◽  
Yoshiko MIZUNO ◽  
Iwao NAKATSUKA ◽  
Akira YOSHITAKE
Keyword(s):  
Renal Failure ◽  
Pharmacokinetic Studies
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