Mitomycin C pharmacokinetics in patients with recurrent or metastatic colorectal carcinoma

1987 ◽  
Vol 65 (3) ◽  
pp. 407-411 ◽  
Author(s):  
Charles Erlichman ◽  
A. Michael Rauth ◽  
Rena Battistella ◽  
Sheldon Fine
Keyword(s):  
Colorectal Carcinoma ◽  
Mitomycin C ◽  
High Performance ◽  
Single Agent ◽  
Area Under The Curve ◽  
Metastatic Colorectal Carcinoma ◽  
Active Metabolites ◽  
Small Component ◽  
Drug Concentrations ◽  
Hplc Technique

The pharmacokinetics of mitomycin C as a single agent have been determined in 25 treatment courses given to 18 patients with recurrent or metastatic colorectal carcinoma using a high performance liquid chromatography (HPLC) assay to analyze plasma and urine samples. The plasma pharmacokinetics conformed to a two-compartment linear model in 21 of 25 courses monitored with a mean t½λ1 of 9.8 ± 1.2 (SEM) min and mean t½λz of 64.1 ± 8.9 (SEM) min. The large variation observed in t½λz was not related to dose or treatment, but an interaction of these two factors approached significance (p = 0.057). Renal excretion in the 12 courses in which it was determined averaged only 2.3% of the total administered dose during the first 4 h monitored and no mitomycin C metabolites were detected in plasma or urine by the HPLC technique used. The most common toxicity, thrombocytopenia, did not correlate with t½λz or the area under the curve. This may be due to (i) a failure to monitor active metabolites of mitomycin C; (ii) other factors besides plasma drug concentrations that mediate toxicity towards marrow elements; or (iii) the small number of courses associated with thrombocytopenia (<100 000/mm3). Our study indicates that (i) an interaction of drug dose and treatment course may be associated with increasing t½λz; (ii) the renal clearance contributes a small component of mitomycin C elimination; (iii) metabolites of mitomycin C cannot be detected by the present HPLC technique; and (iv) routine monitoring of mitomycin C using present methods cannot be recommended for clinical use to predict toxicity.

Mitomycin C, methyl-CCNU and 5-fluorouracil in the treatment of metastatic colorectal carcinoma

1980 ◽  
Vol 5 (1) ◽  
pp. 39-42 ◽  
Author(s):  
Philip D. Bonomi ◽  
Govind Chandra ◽  
Arthur H. Rossof ◽  
David Klaassen
Keyword(s):  
Colorectal Carcinoma ◽  
Mitomycin C ◽  
Metastatic Colorectal Carcinoma

Gastrointestinal Permeability - a Parameter of Possible Prognostic Importance in Metastatic Colorectal Carcinoma

Pteridines ◽  
2008 ◽  
Vol 19 (1) ◽  
pp. 19-22 ◽  
Author(s):  
Bohuslav Melichar ◽  
Radomír Hyspler ◽  
Hana Kalabova ◽  
Lubor Urbanek ◽  
Lenka Krcmova ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Intestinal Permeability ◽  
High Performance ◽  
Prognostic Significance ◽  
Metastatic Colorectal Carcinoma ◽  
Poor Survival ◽  
Systemic Immune Activation ◽  
Prognostic Importance ◽  
Urinary Neopterin ◽  
Gastrointestinal Permeability

Abstract Recently, we have observed in patients with ovarian carcinoma an association between intestinal permeability and prognosis and a correlation between urinary neopterin and parameters of intestinal permeability. In order to examine prognostic significance of intestinal permeability in a different group of patients, we have retrospectively analyzed pretreatment parameters of gastrointestinal permeability and urinary neopterin in 21 consecutive patients with metastatic colorectal carcinoma treated with the combination of cetuximab, irinotecan, leucovorin and 5-fluorouracil. Neopterin was determined by high-performance liquid chromatography, and gastrointestinal permeability was assessed by measuring, using capillary gas chromatography, urinary sucrose, lactulose, xylose, mannitol and sucralose after oral challenge. Pretreatment sucrose/mannitol ratio equal or above 0.04 (median survival 10.6 vs. 18.4 months; p = 0.03), sucrose/xylose equal or above 0.02 (12.1 vs. 19 months; p = 0.04) and urinary neopterin equal or above 220 μmol/mol creatinine (10.6 vs. 18.4 months; p = 0.02) were indicative of poor survival. A significant correlation was observed between urinary neopterin and sucrose/xylose ratio (rs = 0.57, p = 0.007), while correlation between urinary neopterin and sucrose/mannitol ratio (rs = 0.38, p = 0.096) was of borderline significance. In conclusion, present data demonstrate that gastrointestinal permeability is associated with systemic immune activation and may be of prognostic significance in patients with metastatic colorectal carcinoma.

Phase II Study of Capecitabine in Patients With Fluorouracil-Resistant Metastatic Colorectal Carcinoma

2004 ◽  
Vol 22 (11) ◽  
pp. 2078-2083 ◽  
Author(s):  
Paulo M. Hoff ◽  
Richard Pazdur ◽  
Yvonne Lassere ◽  
Susan Carter ◽  
Dvorit Samid ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Sequential Analysis ◽  
Single Agent ◽  
Clinical Activity ◽  
Metastatic Colorectal Carcinoma ◽  
Eligibility Criteria ◽  
Group Sequential ◽  
First Line Therapy ◽  
Kaplan Meier ◽  
Hand Foot Syndrome

Purpose Capecitabine is an oral fluoropyrimidine converted to fluourouracil (FU) preferentially in tumor tissue. It has proven clinical activity against colorectal cancer when used as first-line therapy. The objectives of this study were to assess the safety and efficacy of capecitabine in patients with metastatic colorectal carcinoma who progressed despite previous FU therapy. Patients and Methods According to the group sequential analysis design of this study, accrual would stop if no responses were observed in the first 20 patients treated. If one or more objective responses were confirmed, the trial would be expanded. Patients received capecitabine 1,250 mg/m2 twice a day for 14 days, every 3 weeks. Tumor lesions were assessed every 6 weeks, and patients were followed for survival every 3 months after completing treatment. Results Twenty-three patients were enrolled onto the study; 22 fulfilled all the eligibility criteria. No objective responses were observed among the 22 eligible patients; 11 patients (50%) had stable disease for a median duration of 141 days (range, 88–289 days). The Kaplan-Meier estimate of median time to disease progression was 64 days (95% CI, 41 to 134 days). The median survival time estimate was 389 days (95% CI, 267 to 637 days). The most frequent treatment-related adverse events were hand-foot syndrome, diarrhea, and nausea or vomiting. There were no grade 4 toxicities and no treatment-related deaths. Conclusion Single-agent capecitabine in patients with metastatic colorectal carcinoma refractory to FU showed no objective responses and clinical benefit that was, at best, modest. The use of capecitabine in combination with other treatments in this patient population is under investigation.

scholarly journals Effects of Transcutol P and Precirol ATO-5 on Percutaneous Absorption of Flutamide from Emulgels

2021 ◽  
Author(s):  
Parandis Khalilollah ◽  
Javad Shokri ◽  
Seyedehzahra Ahmadi ◽  
Farnaz Monajjemzadeh
Keyword(s):  
Percutaneous Absorption ◽  
High Performance ◽  
Area Under The Curve ◽  
Diffusion Cell ◽  
Rat Skin ◽  
Androgenic Alopecia ◽  
Absorption Enhancers ◽  
Franz Diffusion Cell ◽  
Drug Concentrations ◽  
Male Pattern

Background: Flutamide is a non-steroidal anti-androgenic agent which is not only used in treating prostate cancer but also can be effective in some disorders such as androgenic alopecia and male pattern baldness. Several serious side effects for systemic administration of flutamide can be overcome by emulgel dosage form. Absorption enhancers can promote permeation of flutamide through skin. Percutaneous absorption of Flutamide emulgels with different concentrations of Transcutol P and Precirol ATO5 was studied. Methods: Various emulgel formulations using different concentration of Transcutol P and Precirol ATO5 with 0.5 to 5 % w/w were prepared. Percutaneous absorption was tested with standard Franz Diffusion Cell equipment using full thickness rat skin. Drug concentrations in the samples were analyzed by High-Performance Liquid Chromatography (HPLC) equipped with UV-Vis detector at 305 nm. Results: The percutaneous absorption of flutamide emulgels formulated with enhancers was higher than control formulations. Enhancement ratio increased from 1.218 to 3.670 and 1.346 to3.900 for Precirol ATO5 and Transcutol P, respectively. Area under the Curve (AUC) increased by increase the enhancers’ concentration and a significant upsurge was seen in the concentration 1% for both enhancers. Conclusion: The flutamide emulgel containing 1% Transcutol P showed more appropriate percutaneous absorption through the skin compared to others.

scholarly journals Efavirenz Pharmacokinetics in Cerebrospinal Fluid and Plasma over a 24-Hour Dosing Interval

2012 ◽  
Vol 56 (9) ◽  
pp. 4583-4585 ◽  
Author(s):  
Aylin Yilmaz ◽  
Victoria Watson ◽  
Laura Dickinson ◽  
David Back
Keyword(s):  
Cerebrospinal Fluid ◽  
High Performance ◽  
Area Under The Curve ◽  
Dosing Interval ◽  
Lumbar Drain ◽  
Chromatography Tandem Mass Spectrometry ◽  
Drug Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
Median Plasma ◽  
Csf Concentration

ABSTRACTWe determined the pharmacokinetics of efavirenz in plasma and cerebrospinal fluid (CSF) over a 24-h dosing interval in a patient who had undergone a lumbar drain because of cryptococcal meningitis. Drug concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry in paired CSF (n= 24) and plasma (n= 25) samples. The median plasma efavirenz concentration was 3,718 ng/ml (range, 2,439 to 4,952), and the median CSF concentration was 16.3 ng/ml (range, 7.3 to 22.3). The CSF/plasma area-under-the-curve ratio was 0.0044 corresponding to a CSF penetration of 0.44% of plasma.

Hepatic artery infusion with 5-fluorouracil and mitomycin-c in metastatic colorectal carcinoma phase ii study

1982 ◽  
Vol 10 (5) ◽  
pp. 463-470 ◽  
Author(s):  
Asgeir Theodors ◽  
Ronald M. Bukowski ◽  
Ian Lavery ◽  
James S. Hewlett ◽  
Robert B. Livingston ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Mitomycin C ◽  
Hepatic Artery ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Hepatic Artery Infusion ◽  
Metastatic Colorectal Carcinoma

scholarly journals Pharmacokinetics of Ertapenem in Healthy Young Volunteers

2002 ◽  
Vol 46 (11) ◽  
pp. 3506-3511 ◽  
Author(s):  
A. K. Majumdar ◽  
D. G. Musson ◽  
K. L. Birk ◽  
C. J. Kitchen ◽  
S. Holland ◽  
...  
Keyword(s):  
Protein Binding ◽  
High Performance ◽  
Dose Range ◽  
Single Agent ◽  
Area Under The Curve ◽  
Reversed Phase ◽  
Men And Women ◽  
The Mean ◽  
Multiple Dose Pharmacokinetics ◽  
Dose Proportional

ABSTRACT Ertapenem (INVANZ) is a new once-a-day parenteral β-lactam antimicrobial shown to be effective as a single agent for treatment of various community-acquired and mixed infections. The single- and multiple-dose pharmacokinetics of ertapenem at doses up to 3 g were examined in healthy young men and women volunteers. Plasma and urine samples collected were analyzed using reversed-phase high-performance liquid chromatography with UV detection. Ertapenem is highly bound to plasma protein. The protein binding changes from ∼95% bound at concentrations of <50 μg/ml to ∼92% bound at concentrations of 150 μg/ml (concentration at the end of a 30-min infusion following the 1-g dose). The nonlinear protein binding of ertapenem resulted in a slightly less than dose proportional increase in the area under the curve from 0 h to infinity (AUC0-∞) of total ertapenem. The single-dose AUC0-∞ of unbound ertapenem was nearly dose proportional over the dose range of 0.5 to 2 g. The mean concentration of ertapenem in plasma ranged from ∼145 to 175 μg/ml at the end of a 30-min infusion, from ∼30 to 34 μg/ml at 6 h, and from ∼9 to 11 μg/ml at 12 h. The mean plasma t 1/2 ranged from 3.8 to 4.4 h. About 45% of the plasma clearance (CLP) was via renal clearance. The remainder of the CLP was primarily via the formation of the β-lactam ring-opened metabolite that was excreted in urine. There were no clinically significant differences between the pharmacokinetics of ertapenem in men and women. Ertapenem does not accumulate after multiple once-daily dosing.

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