Two randomized, double-blind, placebo-controlled, dose-escalation phase 1 studies evaluating BTH1677, a 1, 3-1,6 beta glucan pathogen associated molecular pattern, in healthy volunteer subjects.

Background: BTH1677 is a beta glucan pathogen associated molecular pattern (PAMP) currently being investigated as a novel cancer therapy. Here, the initial safety and pharmacokinetic (PK) results of BTH1677 in healthy subjects are reported.

Subjects And Methods: In the Phase 1a single-dosing study, subjects were randomized (3:1 per cohort) to a single intravenous (i.

Identifying individuals at risk for the development of type 2 diabetes mellitus.

Objective: To describe a population-based approach to the identification of individuals at high risk for the development of type 2 diabetes mellitus (DM).

Study Design: A prospective analysis of the incidence of DM in low- and high-risk groups.

Patients And Methods: Questions associated with the risk of developing DM were incorporated into a health risk assessment (HRA), and health plan members were invited to complete the HRA as part of worksite health promotion efforts or medical clinic visits.

The influence of food on the bioavailability of a twice-daily controlled release carbamazepine formulation.

Carbatrol, a new dosage form of carbamazepine (CBZ), was developed consisting of three different types of pellets (immediate release, controlled release, and enteric release). The objective of this study was to explore the influence of food on absorption of CBZ. This was a randomized, open-label, single-dose crossover study conducted in 12 healthy volunteers.

Improving diabetes care in a large health care system: an enhanced primary care approach.

Objective: The objective of this study was to evaluate the impact of a multifaceted improvement strategy on diabetes quality of care in a defined population of patients.

Study Design: A multifaceted improvement strategy to enhance diabetes care was deployed to 18 primary care clinics serving 170,000 adults. Interventions empowered patient self-management, supported care team decision making, redesigned office systems, and maximized use of available information technology.

Pharmacokinetics and blood pressure response of losartan in end-stage renal disease.

Background: Losartan is a selective angiotensin AT1 receptor antagonist currently employed in the management of essential hypertension. This compound is in common use in populations with renal failure and end-stage renal disease (ESRD).

Objective: To investigate the pharmacokinetics and pharmacodynamics of losartan in patients with ESRD in order to establish administration guidelines.

Pharmacokinetics of flutamide in patients with renal insufficiency.

Aims: The aim of this study was to determine the pharmacokinetic parameters of flutamide, a nonsteroidal antiandrogenic compound, and its pharmacologically active metabolite, hydroxyflutamide, in renal insufficiency. Haemodialysis (HD) clearance of flutamide and hydroxyflutamide was also determined.

Methods: Pharmacokinetic parameters were assessed for flutamide and hydroxyflutamide in 26 male subjects with normal renal function (creatinine clearance by 24 h urine collection, CLcr, greater than 80 ml min(-1) 1.

Pharmacokinetics of oral and intravenous dolasetron mesylate in patients with renal impairment.

In an open-label, randomized, two-way complete crossover study, the influence of renal impairment on the pharmacokinetics of dolasetron and its primary active metabolite, hydrodolasetron, were evaluated. Patients with renal impairment were stratified into three groups of 12 based on their 24-hour creatinine clearance (Cl(cr)): group 1, mild impairment (Cl(cr) between 41 and 80 mL/min); group 2, moderate impairment (Cl(cr) between 11 and 40 mL/min); and group 3, endstage renal impairment (Cl(cr) < or = 10 mL/min). Twenty-four healthy volunteers from a previous study served as the control group.

Effects of probenecid and cimetidine on renal disposition of ofloxacin in rats.

The renal handling of ofloxacin in rats which were given ofloxacin either alone or in combination with probenecid or cimetidine was studied. In the presence of cimetidine or probenecid, ofloxacin's total and renal clearances were reduced and its half-life was prolonged. This suggests that ofloxacin is secreted by both the anionic and cationic transport systems.

Pharmacokinetics of zileuton and its metabolites in patients with renal impairment.

The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance > 90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60-90 mL/min), eight with moderate (creatinine clearance, 30-59 mL/min), and six with severe (creatinine clearance < 30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all participants including those with severe renal impairment and those receiving hemodialysis.

Absolute bioavailability of bromfenac in humans.

Objective: To estimate absolute bioavailability of bromfenac and to compare its pharmacokinetics after intravenous and oral administration.

Design: This was a randomized, open-label, single-dose, crossover study conducted under fasting conditions with a washout period of at least 48 hours between doses. Each subject received a 50-mg dose of bromfenac both intravenously and orally followed by collection of blood samples at specified time intervals.

Determination of residual renal function with iohexol clearance in hemodialysis patients.

Residual renal function (RRF) may contribute significantly to the total dialysis prescription. Conventional quantitation of RRF in hemodialysis (HD) patients is measured by urea clearance and requires a 24-hour urine collection which is often difficult to perform and inaccurate. The renal clearance of iohexol was evaluated as an alternative method for RRF assessment (iohexol-derived RRF) in hemodialysis patients.

Pharmacologic profile of diaspirin cross-linked hemoglobin in hemodialysis patients.

Various hemoglobin compounds have been evaluated as potential oxygen-carrying, blood volume expanders, but toxicity has prevented clinical application. Diaspirin cross-linked hemoglobin (DCLHb) represents a modified hemoglobin compound that is derived from human red blood cells and maintained in a tetrameric configuration by cross-linkages between the two alpha chains of the hemoglobin molecule. In a randomized, placebo-controlled, single-blind, cross-over trial, DCLHb's safety and pharmacologic parameters were evaluated in 18 subjects receiving chronic hemodialytic therapy.

The pharmacokinetics of losartan in renal insufficiency.

Aim: To determine the effect of renal insufficiency on the pharmacokinetics and pharmacodynamics of losartan (MK-954) and its metabolite E3174.

Patients And Methods: A two-center, unblinded trial was performed in 18 patients (age range 31-63 years) with various degrees of renal function grouped according to the renal clearance of creatinine: group I, creatinine clearance > or = 75 ml/min; group II, creatinine clearance 30-74 ml/min; group III, creatinine clearance 10-29 ml/min (n = 6 in all groups). Losartan (100 mg/day) was administered under supervised conditions for seven consecutive days.

Disposition of gabapentin in anuric subjects on hemodialysis.

Gabapentin is an anticonvulsant drug, which in man is cleared solely by renal excretion and is not bound to plasma proteins. Because the clearance of gabapentin is dependent on renal function, the pharmacokinetics of gabapentin were investigated in anuric subjects maintained on hemodialysis. Plasma samples were obtained over an 8-day period after administration of single oral 400-mg doses of gabapentin.

Disposition of misoprostol and its active metabolite in patients with normal and impaired renal function.

The disposition of misoprostol acid, the active metabolite of misoprostol, was studied in 48 subjects with various degrees of renal function after administration of a single 400 microgram oral dose of misoprostol. Subjects were assigned to one of four treatment groups: group 1, normal renal function with creatinine clearance (CLCR) 80-140 mL/min/1.73 m2; group 2, mild renal impairment with CLCR 50-79 mL/min/1.

Pharmacokinetics of bepridil and two of its metabolites in patients with end-stage renal disease.

The pharmacokinetics of bepridil and 2 of its major metabolites (McN-A-2600 and McN-6303) were studied in 6 patients with end-stage renal disease (ESRD) before and after hemodialysis. Patients underwent dialysis 1 day after a single oral 200-mg dose of bepridil hydrochloride; blood was sampled for up to 7 days. The mean (+/- SD) peak plasma concentration, time of peak concentration, and area under the plasma concentration-time curve (0-168 hours) for each agent were as follows: bepridil, 806 +/- 321 ng/mL, 2.

The pharmacokinetics of aminoguanidine in end-stage renal disease patients on hemodialysis.

Aminoguanidine is an investigational agent that may slow or prevent many diabetes-related complications. Since the elimination of aminoguanidine is dependent on renal function, its pharmacokinetics was investigated in eight chronic renal failure patients maintained on hemodialysis. Each patient received 300 mg of aminoguanidine hydrochloride during both an interdialytic and an intradialytic period.

Effects of hemodialysis on plasma protein binding of bepridil.

The effects of end-stage renal disease (ESRD) and hemodialysis on the in vitro plasma protein binding of bepridil hydrochloride were investigated. The possible influence of bepridil metabolites on bepridil-protein binding in ESRD patients was also examined. Plasma samples were obtained from six patients with ESRD.

Pharmacokinetics of tazobactam M1 metabolite after administration of piperacillin/tazobactam in subjects with renal impairment.

Tazobactam is a new derivative of penicillinic acid sulfone, which functions as an irreversible inhibitor of many beta-lactamases. The disposition of tazobactam M1 metabolite after intravenous (i.v.

A dose-ranging pharmacokinetics study of sodium diethyldithiocarbamate in normal healthy volunteers.

Sodium diethyldithiocarbamate (DDTC) is an investigational modulator of the toxicity produced by cisplatin. The pharmacokinetics of DDTC were evaluated after administration of 200 mg/m2/hr (n = 8) and 400 mg/m2/hr (n = 7) DDTC as 4-hour intravenous infusions to normal male healthy volunteers. Diethyldithiocarbamate concentration at steady-state (Cpss) increased disproportionally from 27.

Disposition of Misoprostol and Its Active Metabolite in Impaired Hepatic Function.

The pharmacokinetics of misoprostol and its active metabolite, misoprostol acid, was assessed in 17 healthy subjects and 17 subjects with various degrees of hepatic impairment. Before misoprostol administration, subjects underwent antipyrine and indocyanine green clearance studies to assess hepatic functional capacity. Subjects were administered 400 mcg of oral misoprostol in an open-label design.

Evaluation of two intravenous single-bolus methods for measuring effective renal plasma flow.

This open-label, three-way crossover study examined the feasibility of measuring effective renal plasma flow (ERPF) using a single intravenous (IV) bolus method. Eight healthy young adults (four women aged 28 +/- 5 years [mean +/- SD] and four men aged 30 +/- 7 years) received on separate days an IV bolus of p-aminohippurate (PAH) 10 mg/kg, an IV bolus of phenolsulfonphthalein (PSP) 1 mg/kg, and the standard constant-rate IV infusion of PAH. The renal clearance (CLR) and plasma clearance (CLP) of PAH after constant infusion were 623.

New therapeutic agents in the management of hypertension: angiotensin II-receptor antagonists and renin inhibitors.

Objective: To review the chemistry, pharmacokinetics, and clinical trials of two new classes of antihypertensive drugs, angiotensin II-receptor antagonists and renin inhibitors.

Data Sources: Primary literature on angiotensin II-receptor antagonists and renin inhibitors was identified through a comprehensive medical literature search from 1961 through 1993. This search included journal articles, abstracts, and reports of both animal and human research published in the English language.

Peritoneal dialysis-related peritonitis treatment recommendations. 1993 update. The Ad Hoc Advisory Committee on Peritonitis Management. International Society for Peritoneal Dialysis.

In conclusion, the recommendations provided in this document represent a distillation of various experiences, as well as data obtained from published studies. It is hoped that this compilation will provide a basis upon which future developments and advances can be made in the therapeutic approach to infectious complications of peritoneal dialysis.

The disposition and protein binding of batanopride and its metabolites in subjects with renal impairment.

We have studied the disposition of batanopride and its three major metabolites (the erythro-alcohol, threo-alcohol, and N-desethyl metabolites) in 27 subjects with various degrees of renal function after intravenous infusion of a single dose of 3.6.mg.