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

2003 ◽  
Vol 47 (4) ◽  
pp. 1395-1398 ◽  
Author(s):  
Chin-Chung Lin ◽  
Li-Tain Yeh ◽  
Trong Luu ◽  
David Lourenco ◽  
Johnson Y. N. Lau
Keyword(s):  
Oral Dose ◽  
Oral Administration ◽  
Oral Absorption ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Total Radioactivity ◽  
Cynomolgus Monkeys ◽  
Elimination Half ◽  
Extensive Metabolism ◽  
Total Body

ABSTRACT Absorption, pharmacokinetics, distribution, metabolism, and excretion of [14C]ribavirin were studied in rats (30 mg/kg of body weight) and cynomolgus monkeys (10 mg/kg) after intravenous (i.v.) and oral administration. The oral absorption and bioavailability were 83 and 59%, respectively, in rats and 87 and 55%, respectively, in monkeys. After i.v. administration, the elimination half-life (t [1/2]) was 9.9 h in rats and 130 h in monkeys and the total body clearance was 2,600 ml/h/kg in rats and 224 ml/h/kg in monkeys. The apparent volume of distribution was 11.4 liter/kg in rats and 29.4 liter/kg in monkeys. There was extensive distribution of drug-derived radioactivity into red blood cells and extensive metabolism of ribavirin in rats and a lesser degree of metabolism in monkeys. Excretion of total radioactivity in urine from rats accounted for 84% of the i.v. dose and 83% of the oral dose, whereas that from monkeys accounted for 47% of the i.v. dose and 67% of the oral dose. Several metabolites were observed in plasma and urine from both species. The amount of unchanged ribavirin in urine from both species was quite small after either i.v. or oral administration.

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.

scholarly journals Single-Dose Pharmacokinetics and Metabolism of [14C]Remofovir in Rats and Cynomolgus Monkeys

2005 ◽  
Vol 49 (3) ◽  
pp. 925-930 ◽  
Author(s):  
Chin-Chung Lin ◽  
Christine Xu ◽  
Nanqun Zhu ◽  
David Lourenco ◽  
Li-Tain Yeh
Keyword(s):  
Single Dose ◽  
Oral Dose ◽  
Oral Administration ◽  
Oral Absorption ◽  
Urinary Metabolites ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Total Radioactivity ◽  
Fecal Excretion ◽  
Total Body

ABSTRACT Single-dose pharmacokinetics and metabolism of [14C]remofovir was studied in rats and monkeys following intravenous (i.v.) and oral administration (30 mg/kg of body weight). Oral absorption and bioavailability were 29.7 and 5.42% in rats and 65.6 and 19.4% in monkeys, respectively. Following i.v. administration, the elimination half-life for remofovir was 0.7 h in both rats and monkeys. Total body clearance was 5.85 liters/h/kg in rats and 2.60 liters/h/kg in monkeys; apparent volume of distribution was 5.99 liters/kg in rats and 2.70 liters/kg in monkeys. Following oral administration, remofovir was extensively converted to 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and other metabolites in both species. In rats, excretion of total radioactivity in urine accounted for 61.8% of the i.v. dose and 12.9% of the oral dose, while in monkeys it accounted for 43.3% of the i.v. dose and 34.9% of the oral dose. Following i.v. dosing of [14C]remofovir, fecal excretion of radioactivity accounted for 37.5% of the dose in rats and 17.4% of the dose in monkeys, indicating significant biliary excretion of the drug in animals. PMEA and metabolite A were the major urinary metabolites in both species after i.v. and oral administration of remofovir.

Individualization of Theophylline Dosage in Adults with Bronchial Asthma

1986 ◽  
Vol 20 (9) ◽  
pp. 704-707 ◽  
Author(s):  
Maria J. Otero ◽  
Miguel Barrueco ◽  
Eduardo L. Marino ◽  
Francisco Gomez ◽  
Alfonso Dominguez-Gil
Keyword(s):  
Elderly Patients ◽  
Bronchial Asthma ◽  
Total Body Clearance ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Dosage Regimens ◽  
Elimination Half ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Body Clearance

The influence of age on the disposition of theophylline was studied in 95 adult patients (nonsmokers) with bronchial asthma requiring oral theophylline therapy: 17 patients age ≥39 years, 50 patients age 40–59 years, and 28 patients < 60 years. A decrease was observed in total body clearance together with an increase in the elimination half-life of theophylline parallel to the advance in age of the patients. The apparent volume of distribution of theophylline was similar in the three groups of patients. According to the results obtained, recommendations are made regarding the dosage regimens of theophylline in elderly patients.

Pharmacokinetics of Marbofloxacin Following Oral Administration in Piperine, Quercetin Alone and Both in Combination Pretreated Broiler Chickens

2021 ◽  
Author(s):  
H.B. Patel ◽  
U.D. Patel ◽  
C.M. Modi ◽  
V.C. Ladumor ◽  
C.N. Makwana ◽  
...  
Keyword(s):  
Oral Administration ◽  
Broiler Chickens ◽  
High Performance ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Metabolizing Enzymes ◽  
Single Oral Administration ◽  
Elimination Half ◽  
Combined Pretreatment ◽  
Apparent Volume Of Distribution

Background: Various antibacterial drugs are substrates for drug metabolizing enzymes. They suffer from reduced bioavailability after oral administration in chickens. Herbal bio-enhancers increased the absorption of co-administered drugs. Hence, present study was planned to explore the bio-enhancing effect of piperine and quercetin pretreatment on pharmacokinetics of marbofloxacin after oral administration in broiler chickens.Methods: The pharmacokinetics of marbofloxacin was investigated following single dose (5 mg/kg) oral administration in piperine, quercetin alone and both in combination pretreated (10 mg/kg each, oral, 3 days) broiler chickens. The concentrations of marbofloxacin in plasma samples were analyzed by high performance liquid chromatography.Result: Following single oral administration of marbofloxacin, elimination half-lives (t1/2β) were 6.23 ± 1.01, 5.69 ± 0.39 and 7.71 ± 0.59 h in piperine, quercetin and both in combination pretreated chickens, respectively. The elimination half-life (t1/2β), apparent volume of distribution (Vd(area)/F) and mean residence time (MRT) were significantly (p less than 0.05) higher in combination pretreated chickens as compared to piperine and quercetin alone groups. Piperine and quercetin combined pretreatment has improved the pharmacokinetics profile of marbofloxacin after oral administration in broiler chickens. Findings of the study are expedient for the development of protocol for use of bio-enhancers with antibiotics in broiler chickens.

scholarly journals Intravascular plasma disposition and salivary secretion of closantel and rafoxanide in sheep

1999 ◽  
Vol 70 (2) ◽  
Author(s):  
G.E. Swan ◽  
H.A. Koeleman ◽  
H.S. Steyn ◽  
M.S.G. Mülders
Keyword(s):  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Salivary Secretion ◽  
Volume Of Distribution ◽  
Large Individual ◽  
Drug Plasma ◽  
Elimination Half ◽  
Proportional Increase ◽  
Total Body ◽  
Apparent Volume Of Distribution

The plasma and salivary disposition of closantel and rafoxanide were examined following intravenous administration in adult sheep. Two studies were conducted with rafoxanide at 7.5 mg/kg and 1 with closantel using 2 doses (5 and 15 mg/kg). The pharmacokinetic profile of both drugs in plasma were best described by a 2-compartmental model with 1st-order rate constants. Plasma disposition of closantel and rafoxanide were characterised by a rapid distribution (t1/2(a) of <30 min), long elimination half-life (t1/2(b) of 17.0 + 4.0 days for closantel and 7.2 + 0.6 days for rafoxanide), small apparent volume of distribution (Vss of <0.15 ℓ/kg) and a slow rate of total body clearance (Cl of <0.01mℓ/min/kg). The area under the drug plasma concentration curve (AUC) of closantel at 5 mg/kg was nearly twice as large as that of rafoxanide at 7.5 mg/kg resulting from the slower t1/2(b) observed with closantel compared to rafoxanide. Large individual differences were observed in the rate measurements of distribution (k12, k21 and t1/2(a)), whereas the parameters of elimination (k10, t1/2(b) and Cl), were more consistent between animals. A dose proportional increase in AUC was observed for closantel administered at 5 and 15 mg/kg. A low, constant salivary concentration of closantel (mean of 0.04+0.05 mg/mℓ) and rafoxanide (mean of 0.07+0.04 mg/mℓ) was observed during the 24-h examination period after dosing.

Toxicokinetics of Colchicine in Humans: Analysis of Tissue, Plasma and Urine Data in Ten Cases

1992 ◽  
Vol 11 (6) ◽  
pp. 510-516 ◽  
Author(s):  
M. Rochdi ◽  
A. Sabouraud ◽  
F.J. Baud ◽  
C. Bismuth ◽  
J.M. Scherrmann
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Post Mortem ◽  
Elimination Half ◽  
High Concentrations ◽  
Human Poisoning ◽  
Total Body ◽  
Therapeutic Doses ◽  
Kinetics Of

1 A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2 Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 131 h-1 and three-fold less than total body clearance (391 h-1). The apparent volume of distribution was 211 kg-1. 3 Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g -1); it was also found in the brain (125 ng g-1). 4 This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occuring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.

scholarly journals Bioavailability pharmacokinetics and residues of marbofloxacin in normal and E.coli infected broiler chicken

2016 ◽  
Vol 4 (2) ◽  
pp. 144
Author(s):  
Ashraf El-Komy ◽  
Taha Attia ◽  
Amera Abd El Latif ◽  
Hanem Fathy
Keyword(s):  
Oral Administration ◽  
Half Life ◽  
Broiler Chickens ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Serum ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Total Body

The pharmacokinetics of marbofloxacin was studied following a single intravenous, oral administration in normal broiler chickens and repeated oral administrations in normal and experimentally E.coli infected broiler chickens. The pharmacokinetic parameters following a single intravenous injection of 2 mg/kg b.wt., revealed that marbofloxacin obeyed a two compartments open model, distribution half-life (t0.5(α)) was 0.25±0.02 h, volume of distribution (Vdss) was 0.76±0.08 L/kg, elimination half-life (t0.5(β)) was 5.43±0.87 h and total body clearance (CLtot) was 0.09±0.002 l/kg/h. Following a single oral administration, marbofloxacin was rapidly and efficiently absorbed through gastrointestinal tract of chickens as the absorption half-life (t0.5 (ab): 0.62±0.02 h). Maximum serum concentration (Cmax) was 1.15±0.01 μg/ml, reached its maximum time (tmax) at 2.53±0.04 h, elimination half-life (t0.5 (el)) was 7.36±0.20 h indicating the tendency of chickens to eliminate marbofloxacin in slow rate. Oral bioavailability was 73.57± 1.90 % indicating good absorption of marbofloxacin after oral administration. Serum concentrations of marbofloxacin following repeated oral administration of 2 mg/kg b.wt. once daily for five consecutive days, peaked 2 hours after each oral dose with lower significant values recorded in experimentally infected broiler chickens than in normal ones. Tissues residues of marbofloxacin in slaughtered normal chickens was highly in those tissues lung, liver, and kidneys in chickens and the chicken must not be slaughtered before 3 days of stopping of drug administration. It was concluded that the in- vitro protein binding was 12.33±0.82%.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

Half-life, hemodynamic, renal, and hormonal effects of prorenin in cynomolgus monkeys

1991 ◽  
Vol 260 (4) ◽  
pp. R804-R810 ◽  
Author(s):  
T. Lenz ◽  
J. E. Sealey ◽  
T. Maack ◽  
G. D. James ◽  
R. L. Heinrikson ◽  
...  
Keyword(s):  
Half Life ◽  
Renal Plasma Flow ◽  
Plasma Renin ◽  
Apparent Volume ◽  
Reproductive Organs ◽  
Volume Of Distribution ◽  
Plasma Testosterone ◽  
Metabolic Clearance ◽  
Cynomolgus Monkeys ◽  
Pharmacokinetic Properties

Prorenin is found in human plasma, kidneys, and reproductive organs. We investigated the physiological and pharmacokinetic properties of plasma prorenin, and its plasma conversion to active renin, by bolus infusions of human recombinant prorenin (0.5, 2, 20 micrograms; n = 4/dose) into anesthetized male cynomolgus monkeys. The infused prorenin had 3% intrinsic renin activity. Plasma prorenin rose from 61 +/- 6 to 101 +/- 11, 570 +/- 46, and 7,700 +/- 390 ng.ml-1.h-1, respectively, after 5 min. Plasma renin increased to 3% of total renin, angiotensin II increased less than twofold, and aldosterone did not change. Plasma testosterone fell slightly (P less than 0.01). Mean arterial pressure (MAP) fell slowly from 104 +/- 3 to 93 +/- 3 mmHg at 60 min (P less than 0.001). Heart rate, glomerular filtration rate, renal plasma flow, and urinary sodium and potassium excretion were unchanged. For the 2- and 20-micrograms doses, respectively, effective half-life of plasma decay was 47 +/- 4.9 and 109 +/- 21 min (P less than 0.05), apparent volume of distribution was 145 +/- 11 and 166 +/- 35 ml/kg, and metabolic clearance rate was 2.30 +/- 0.44 and 1.08 +/- 0.14 ml.min-1.kg-1 (P less than 0.01). In conclusion, neither the hormonal nor the physiological response to infusion of pharmacologic levels of recombinant human prorenin into monkeys provide evidence for conversion of circulating prorenin to renin. MAP did not increase and actually fell without commensurate effects on renal function. The half-life of recombinant prorenin was similar to that of renin.

Inhibitory effect of phenelzine on oxidative microsomal enzyme systems of rat liver

1983 ◽  
Vol 61 (5) ◽  
pp. 524-529 ◽  
Author(s):  
P. M. Bélanger ◽  
A. Atitsé-Gbeassor
Keyword(s):  
Rat Liver ◽  
Apparent Volume ◽  
Inhibitory Effect ◽  
Volume Of Distribution ◽  
Inhibitory Effects ◽  
Oxidative Reactions ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Cytochrome P 450 ◽  
Substrate Addition

The inhibitory effects of phenelzine on the hepatic microsomal demethylation of aminopyrine, N,N-dimethylaniline, and p-nitroanisole on the hydroxylation of aniline and on the pharmacokinetics of antipyrine were investigated in the rat. Phenelzine produced a competitive and noncompetitive inhibition of the demethylation of p-nitroanisole and N,N-dimethylaniline, respectively, but was a mixed-type inhibitor of the aminopyrine N-demethylase and aniline hydroxylase. The inhibition constant, Ki, varied between 0.06 to 0.25 mM depending on the substrate used. Preincubation of phenelzine for 30 min with the microsomal homogenate prior to substrate addition doubled its inhibitory effect. Phenelzine induced a type II spectral change when combined with oxidized cytochrome P-450 with a Ks value of 0.4 mM. The administration of one dose of 50 mg∙kg−1 of phenelzine sulfate concomitantly with 50 mg∙kg−1 of antipyrine resulted in a significant decrease of the serum elimination of antipyrine. The serum half-life, apparent volume of distribution, and total body clearance of antipyrine were modified to 3.6 h, 294.1 mL∙kg−1, and 56.8 mL∙h−1∙kg−1, respectively, from 1.5 h, 666.7 mL∙kg−1, and 312.5 mL∙h−1∙kg−1 when antipyrine was administered alone. It is concluded that the inhibitory effect of phenelzine on the microsomal oxidative reactions of rat liver is related to its interaction with cytochrome P-450.

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