Irene Ferreira

The pharmacokinetics of irbesartan in renal failure and maintenance hemodialysis

An open‐label, multiple‐dose, parallel‐group study was conducted to evaluate the pharmacokinetics of the angiotensin II receptor antagonist irbesartan in subjects with varying degrees of renal function.

Bioavailability and phase II study of oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer

Purpose: This study was undertaken to address the influence of concurrent administration on the pharmacokinetics of UFT (uracil plus tegafur) and leucovorin (LV), and to measure the antitumor activity of a 28-consecutive-day oral regimen of UFT plus LV in patients with relapsed or refractory colorectal cancer. Methods: Patients with advanced measurable colorectal cancer who had failed previous therapy with intravenous bolus 5-fluorouracil (5-FU) were eligible. Patients were treated with UFT 300 mg/m2 per day plus LV 90 mg per day in three divided doses every 8 h for 28 days, repeated at 35-day intervals. In addition, a three-treatment by three-period crossover bioavailability comparison of oral LV 30 mg plus UFT 200 mg versus either LV or UFT alone was scheduled for the 8 days preceding the first cycle of therapy. Results: Of 19 patients enrolled, 18 were assessable for pharmacokinetics and response. When LV was coadministered with UFT, there were no statistically significant effects on tegafur, uracil, or 5-FU Cmax, AUC, or Tmax, with the exception of a delayed Tmax for tegafur (P = 0.03). No statistically significant differences were found in LV and 5-methyltetrahydrofolate plasma levels when LV was administered alone or with UFT. However, wide interpatient variability was observed for all parameters. There were no antitumor responses seen. Conclusions: Although the Tmax for tegafur is delayed with the concurrent administration of LV, there were no differences (P > 0.05) in any pharmacologic parameters that are of likely clinical significance. However, the great interpatient variability observed in UFT and LV pharmacology may have obscured true bioavailability effects in this small patient population. Daily oral UFT plus LV is inactive as second-line therapy in patients who have failed bolus 5-FU.

Disposition and safety of omapatrilat in subjects with renal impairment

Omapatrilat, a vasopeptidase inhibitor, preserves natriuretic peptides and inhibits the renin angiotensin aldosterone system by simultaneously inhibiting neutral endopeptidase and angiotensinconverting enzyme.

Omapatrilat Increases Key Vascular/Renal Markers Regardless Of Renal Function

Clinical Pharmacology & Therapeutics (1999) 65, 131–131; doi:

Steady-State PK of Omapatrilat in Healthy Subjects

Clinical Pharmacology & Therapeutics (1999) 65, 133–133; doi:

The Effects of Renal Function on PK of Omapatrilat

Clinical Pharmacology & Therapeutics (1999) 65, 134–134; doi:

Omapatrilat: Neurohormonal and Pharmacodynamic Profile When Administered with Furosemide

Pharmacodynamic effects of combination therapy with omapatrilat and furosemide were evaluated. Two groups of 13 healthy subjects each received furosemide 20 mg daily for 15 days coadministered with either placebo on days 6 to 15 or omapatrilat 10 mg on days 6 to 10 and 25 mg on days 11 to 15. In the omapatrilat group, urinary excretion of atrial natriuretic peptide increased, and greater blood pressure reductions were seen compared with placebo. Concomitant omapatrilat treatment did not affect the acute diuresis, natriuresis, and kaliuresis observed with chronic administration of furosemide. Neither effective renal plasma flow nor glomerular filtration rate changed in either treatment group. No clinically significant safety issues were observed. Daily coadministration of omapatrilat 10 or 25 mg with furosemide 20 mg does not affect the pharmacodynamics of furosemide at steady state.

Safety, Absolute Bioavailability, and Dose Proportionality of BMS-181885 (I), A Novel 5HT1, Agonist, Following Intranasal (IN) Dosing in Humans

Clinical Pharmacology & Therapeutics (1999) 65, 130–130; doi: