scholarly journals Pharmacokinetics of trovafloxacin (CP-99,219), a new quinolone, in rats, dogs, and monkeys.

1996 ◽  
Vol 40 (3) ◽  
pp. 561-566 ◽  
Author(s):  
R Teng ◽  
D Girard ◽  
T D Gootz ◽  
G Foulds ◽  
T E Liston
Keyword(s):  
Body Weight ◽  
Bile Duct ◽  
Intravenous Administration ◽  
Biliary Excretion ◽  
Oral Bioavailability ◽  
Serum Proteins ◽  
Unchanged Drug ◽  
Elimination Half ◽  
Oral Doses ◽  
Volumes Of Distribution

The pharmacokinetics of trovafloxacin [CP-99,219; 7-(3-azabicyclo[3.1.0]hexyl)-naphthyridone] were studied in rats, dogs, and monkeys following oral and intravenous administration. After intravenous dosing, the systemic clearances of trovafloxacin in rats, dogs, and monkeys were 12.5, 11.1, and 7.2 ml/min/kg of body weight, respectively, and the respective volumes of distribution were 0.9, 1.7, and 4.3 liters/kg, with corresponding elimination half-lives of 0.7, 1.8, and 7.0 h. After the administration of oral doses of 50, 20, and 20 mg/kg to rats, dogs, and monkeys serum trovafloxacin concentrations reached a maximum at 0.6, 2.3, and 2.3 h, respectively, with respective maximum concentrations of trovafloxacin in serum of 11.5, 3.5, and 5.2 micrograms/ml; the corresponding elimination half-lives were 2.2, 2.5, and 7.5 h. The oral bioavailability of trovafloxacin was 68, 58, and 85% in rats, dogs, and monkeys, respectively. The binding of trovafloxacin to serum proteins was concentration independent, averaging 92, 75, and 66% for rats, dogs, and monkeys, respectively. Trovafloxacin penetrated well into tissues in dogs. The urinary recoveries of unchanged drug were less than 5% in dogs and monkeys, with or without incubation with alkali or Glusulase (beta-glucuronidase and sulfatase). In rats, 99.8% of the orally administered radioactivity was recovered in feces, while 20.6, 3.4, and 67.1% of the radioactive dose in bile duct-cannulated rats were recovered in feces, urine, and bile, respectively. These results suggest that the elimination of trovafloxacin from rats, and possibly from dogs and monkeys, is primarily through biliary excretion.

scholarly journals Pharmacokinetics and Metabolism of [14C]Viramidine in Rats and Cynomolgus Monkeys

2003 ◽  
Vol 47 (8) ◽  
pp. 2458-2463 ◽  
Author(s):  
Chin-Chung Lin ◽  
Kenneth Luu ◽  
David Lourenco ◽  
Li-Tain Yeh
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
Oral Administration ◽  
Oral Absorption ◽  
Total Radioactivity ◽  
Cynomolgus Monkeys ◽  
Elimination Half ◽  
Total Body ◽  
Volumes Of Distribution

ABSTRACT The pharmacokinetics of [14C]viramidine, a prodrug of ribavirin, were studied in rats (30 mg/kg of body weight) and monkeys (10 mg/kg) following intravenous (i.v.) and oral administration. The levels of oral absorption and bioavailabilities were 61.7 and 9.91%, respectively, in rats and 43.9 and 13.6%, respectively, in monkeys. Following i.v. administration, the elimination half-lives were 2.7 h in rats and 28.9 h in monkeys. Total body clearances were 14.0 liters/h/kg in rats and 1.23 liters/h/kg in monkeys; the apparent volumes of distribution were 15.6 liters/kg in rats and 18.6 liters/kg in monkeys. Following oral administration, viramidine was extensively converted to ribavirin, followed by further metabolism of ribavirin in both species, with a faster rate of metabolism in rats than in monkeys. In rats, excretion of total radioactivity in urine accounted for 77.0% of the i.v. dose and 60.8% of the oral dose, while in monkeys it accounted for 44.4% of the i.v. dose and 39.0% of the oral dose. The amount of unchanged viramidine and ribavirin in urine was small in both species after i.v. and oral administration of viramidine.

Oral Pharmacokinetics of Fluazifop-Butyl in Human Volunteers

1991 ◽  
Vol 10 (1) ◽  
pp. 39-43 ◽  
Author(s):  
B.H. Woollen ◽  
T.B. Hart ◽  
P.L. Batten ◽  
W.J.D. Laird ◽  
D.S. Davies ◽  
...  
Keyword(s):  
Body Weight ◽  
Active Ingredient ◽  
Half Life ◽  
Pharmacokinetic Model ◽  
Serum Proteins ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Elimination Half ◽  
Human Volunteers ◽  
Oral Pharmacokinetics

1 Fluazifop-butyl, the active ingredient of FUSILADE, a selective herbicide, was administered orally to three male volunteers at a dose level of 0.07 mg kg-1 body weight. Over a period of 6 d between 80 and 93% of the dose was excreted in urine as the metabolite fluazifop, the majority within the first 24 h. Peak plasma concentrations of fluazifop occurred 1-2.5 h after administration. 2 The elimination of fluazifop from plasma and urine can be described by a one-compartment pharmacokinetic model and the elimination half-life was estimated from blood and urine data to be within the range 9-37 h. Fluazifop was found to bind to serum proteins. 3 The study indicates that the amount of fluazifop-butyl absorbed in exposed persons can be assessed by measuring fluazifop concentrations in urine.

Aztreonam Biliary Excretion in Bile Duct Ligated Jaundiced Rats

1991 ◽  
Vol 3 (2) ◽  
pp. 98-100 ◽  
Author(s):  
F. Rulli ◽  
M. Muzi ◽  
E. Zanella ◽  
P. Cipriani ◽  
A. Magni ◽  
...  
Keyword(s):  
Bile Duct ◽  
Biliary Excretion

Transhepatic absorption and biliary excretion of insulin

1987 ◽  
Vol 65 (9) ◽  
pp. 1982-1987 ◽  
Author(s):  
Walter Zingg ◽  
Aron M. Rappaport ◽  
Bernard S. Leibel
Keyword(s):  
Intravenous Administration ◽  
Biliary Excretion ◽  
Venous Blood ◽  
Intraperitoneal Administration ◽  
Liver Cells ◽  
Insulin Concentration ◽  
Secretory Process ◽  
Insulin Administration ◽  
Hepatic Cells ◽  
Liver Surface

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.

Heparin pretreatment suppresses norepinephrine concentrations in dogs in endotoxic shock.

1977 ◽  
Vol 23 (7) ◽  
pp. 1346-1347 ◽  
Author(s):  
D F Devereux ◽  
C A Michas ◽  
S Rice
Keyword(s):  
Body Weight ◽  
Intravenous Administration ◽  
Endotoxic Shock ◽  
Isotonic Saline ◽  
Control Group ◽  
E Coli ◽  
Physiological Variables ◽  
Blood Pressures

Abstract Mongrel dogs were treated intravenously with either 1000 units of beef-lung heparin per kilogram of body weight or with isotonic saline, before intravenous administration of E. coli endotoxin. We found significant differences in circulating norepinephrine concentrations between a heparin-pretreatment group (1.89 +/- 0.39 microgram/liter) and the control group (9.83 +/- 4.64 microgram/liter), but none with respect to epinephrine. Systolic blood pressures at 360 min were also significantly (P less than 0.05) different, 148 +/- 6 mmHg as compared with 118 +/- 13.4 mmHg. Evidently heparin pretreatment can decrease circulating norepinephrine concentrations in the endotoxic state and changes in circulating catecholamine concentrations can affect physiological variables.

scholarly journals Population pharmacokinetic study of teicoplanin in severely neutropenic patients.

1996 ◽  
Vol 40 (5) ◽  
pp. 1242-1247 ◽  
Author(s):  
O Lortholary ◽  
M Tod ◽  
N Rizzo ◽  
C Padoin ◽  
O Biard ◽  
...  
Keyword(s):  
Steady State ◽  
Trough Concentration ◽  
Linear Regression Analysis ◽  
Central Compartment ◽  
Population Pharmacokinetic ◽  
Mixed Effect ◽  
Elimination Half ◽  
Neutropenic Patients ◽  
The Mean ◽  
Volumes Of Distribution

The teicoplanin pharmacokinetics (PK) of 30 febrile and severely neutropenic patients (polymorphonuclear count, < 500/mm3) with hematologic malignancies were compared with those determined for five healthy volunteers (HV). Neutropenic patients were given piperacillin combined with amikacin, and teicoplanin was added to the regimen the day fever developed in patients suspected of having a staphylococcal infection or 48 h later. Teicoplanin was given intravenously at a dosage of 6 mg/kg of body weight at 0, 12, and 24 h and once a day thereafter. Five to eleven blood samples per patient were collected. Teicoplanin concentrations were measured by liquid chromatography. A bicompartmental model was fitted to the data by a nonlinear mixed-effect-model approach. Multiple-linear regression analysis was applied in an attempt to correlate PK parameters to nine covariates. The mean trough concentrations of teicoplanin 48 h after the onset of treatment and 24 h after the last injection (last trough) +/- standard deviations were 8.8 +/- 4.1 and 17.5 +/- 13.5 mg/liter, respectively. A significant increase was noted in the mean rate of elimination clearance of teicoplanin in neutropenic patients compared with that of HV (0.86 versus 0.73 liter/h, P = 0.002), as was the case with rates of distribution clearance (5.89 versus 4.94 liter/h, P = 0.002); the mean half-life of distribution was significantly shorter in patients than in HV (0.43 versus 0.61 h, P = 0.002). In contrast, the volumes of the central compartment (ca. 5.8 liters for both groups), the volumes of distribution at steady state (HV, 37.6 liters; patients, 55.9 liters), and the elimination half-lives (HV, 39.6 h; patients, 52.7 h) were not significantly different between HV and neutropenic patients. Interindividual variabilities of rates of clearance (coefficient of variation [CV], 43%) and elimination half-lives (CV, 56%) were mainly explained by the variabilities among rates of creatinine clearance. Interindividual variabilities of the volumes of the central compartment (CV, 33%) and the volumes of distribution at steady state (CV = 51%) were correlated to interindividual variabilities among numbers of leukocytes and the ages of patients, respectively. On the basis of the population PK model of teicoplanin, simulations were made to optimize the dosing schedule. A supplemental 6 mg/kg dose of teicoplanin at 36 h resulted in a trough concentration at 48 h of 16.0 +/- 4.5 mg/liter, with only 7% of patients having a trough concentration of less than 10 mg/liter, compared with 46% of patients on the usual schedule.

scholarly journals Treatment of gastrointestinal cytomegalovirus infection with twice-daily foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients with AIDS.

1997 ◽  
Vol 41 (6) ◽  
pp. 1226-1230 ◽  
Author(s):  
D T Dieterich ◽  
M A Poles ◽  
E A Lew ◽  
S Martin-Munley ◽  
J Johnson ◽  
...  
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Gastrointestinal Disease ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Open Label ◽  
Laboratory Observation ◽  
Patient Reports ◽  
Elimination Half ◽  
Days Of Therapy

Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients.

Biliary Excretion of Iodipamide and Iodoxamate in Normal and Common Bile Duct-Obstructed Dogs

1978 ◽  
Vol 13 (3) ◽  
pp. 255-263 ◽  
Author(s):  
FRANCIS A. BURGENER ◽  
HARRY W. FISCHER ◽  
THEODORE D. KENYON
Keyword(s):  
Bile Duct ◽  
Common Bile Duct ◽  
Biliary Excretion

scholarly journals Antischistosomal Activities of Mefloquine-Related Arylmethanols

2012 ◽  
Vol 56 (6) ◽  
pp. 3207-3215 ◽  
Author(s):  
Katrin Ingram ◽  
William Ellis ◽  
Jennifer Keiser
Keyword(s):  
Body Weight ◽  
Worm Burden ◽  
Structural Features ◽  
Content Type ◽  
Antischistosomal Activity ◽  
Oral Doses ◽  
Related Compounds ◽  
Insight Into

ABSTRACTInteresting antischistosomal properties have been documented for the antimalarial mefloquine, a 4-quinolinemethanol. We evaluated the antischistosomal activities of nine mefloquine-related compounds belonging to the 4-pyridinemethanols, 9-phenanthrenmethanols, and 4-quinolinemethanols. Eight compounds revealed high activities againstSchistosoma mansoni in vitro, with two drugs (the 4-quinolinemethanols WR7573 and WR7930) characterized by significantly lower half-maximal inhibitory concentrations (IC50s) (2.7 and 3.5 μM, respectively) compared to mefloquine (11.4 μM). Mefloquine and WR7930 showed significantly decreased IC50s when incubated in the presence of hemoglobin. High worm burden reductions (WBR) were obtained with enpiroline (WBR, 82.7%; dosage, 200 mg/kg of body weight) and itsthreoisomers (+)-threo(WBR, 100%) and (−)-threo(WBR, 89%) and with WR7930 (WBR, 87%; dosage, 100 mg/kg) against adultS. mansoniin mice. Furthermore, excellentin vitroandin vivoantischistosomal activity was observed for two WR7930-related structures (WR29252 and WR7524). In addition, mefloquine (WBR, 81%), enpiroline (WBR, 77%), and WR7930 (WBR, 100%) showed high activities againstS. haematobiumharbored in mice following single oral doses of 200 mg/kg. These results provide a deeper insight into the structural features of the arylmethanols that rule antischistosomal activity. Further studies should be launched with enpiroline and WR7930.

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