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.

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.

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.

scholarly journals Pharmacokinetics of sodium meclofenamate in pre-ruminant cattle

2004 ◽  
Vol 56 (6) ◽  
pp. 695-700
Author(s):  
E.J. Picco ◽  
D.C. Diaz David ◽  
T. Encinas ◽  
M.R. Rubio ◽  
J.C. Boggio
Keyword(s):  
High Performance ◽  
Pharmacokinetic Profile ◽  
Apparent Volume ◽  
Antiinflammatory Drug ◽  
Volume Of Distribution ◽  
Intramuscular Administration ◽  
Flip Flop ◽  
Elimination Phase ◽  
Distribution Phase ◽  
Apparent Volume Of Distribution

The pharmacokinetic profile of sodium meclofenamate, a non-steroidal antiinflammatory drug, was determined in six pre-ruminant calves after intravenous and intramuscular administration at a dose of 2.2mg/kg of body weight. Meclofenamate concentrations were measured using a high performance liquid chromatography assay. The pharmacokinetics of sodium meclofenamate after intravenous and intramuscular administration to calves were characterised by a rapid distribution phase (t½alpha ), 15.45± 4.85min and 23.14± 7.24min for the intravenous and intramuscular administration, respectively, followed by a longer elimination phase (t½beta ) after intramuscular treatment (17.55± 6.52h.). The apparent volume of distribution (Vd) of the drug after intravenous administration was moderate (0.72± 0.12l/kg), and high (3.51± 1.05l/kg) after intramuscular administration. This can be explained by the flip-flop effect or by enterohepatic shunting. The bioavailability achieved after intramuscular administration was 61%.

PHARMACOKINETICS OF EN0XAPARIN AFTER SINGLE SUBCUTANEOUS ADMINISTRATION OF INCREASING DOSES (20 UP TO 80 MG) TO HEALTHY VOLUNTEERS

1987 ◽  
Author(s):  
L Bara ◽  
Y Le Roux ◽  
M Woler ◽  
F Chauliac ◽  
A Frydman ◽  
...  
Keyword(s):  
Subcutaneous Administration ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Thrombin Time ◽  
Mean Values ◽  
Elimination Half ◽  
Heparin Plasma ◽  
The Mean ◽  
The One ◽  
Apparent Volume Of Distribution

The pharmacokinetics of enoxaparin (E) was randomly studied in 12 healthy male volunteers. Each dose (20-40-60 and 80 mg) was injected via subcutaneous (sc) route with a one-week wash out period. Anti-Xa and anti-IIa activities (ACT), calcium thrombin time (CTT) and Heptest were measured over a 36 hour period. E and the IV th International Heparin Standard were both used as internal standards.The anti IIa and CTT effects were only measurable when the injected dose was higher than 40 mg. The maximum anti-Xa and anti-IIa ACT were obtained 3 to 4 hours after the dose. As anti-IIa ACT is lower than anti-Xa ACT (anti-Xa/anti-IIa ACT ration I .6 to 2), the complete pharmacokinetic description of E was only based on anti-Xa data. Thus, the mean values of the maximal anti-Xa ACT (A max) were respectively: 1.58 ± 0.35 pg/ml; 3.83 ± 0.98 jig/ml, 5.38 ± 0.75 ug/ml and 7.44 ± 1.4 pg/ml for the four doses (20-40-60 and 80 mg). The resorption of E after sc injection was strictly linear whereas the relationships between A max or AUC in the one hand and dose in the other hand were A (anti Xa) Max = 0.0954 (dose) - 0,2083 r = 0.9146/p < 0.001; n = 48) and AUC (0 - 36 h) = 0.9117 (dose) - 7.59 (r = 0.9133/p < 0.001; n = 48). The mean residence time of E was close to 6 h (5.83 ± 0.86 h for D = 40 mg; 6.19 ± 0.74 h for D = 60 mg and 6.44 ± 0.76 h for 80 mg) indicating that around 50% of the total anti Xa ACT is induced in a 6 hour interval. The apparent volume of distribution V is close to 61 (6.59 1 ±1.33 1 for D = 60 mg) and the total Dody clearance is equal to 1.25 1/h, indicating the rate of depolymerisation of enoxaparin is lower than that of heparin. Plasma elimination half-life of anti-Xa ACT is equal to 4.36 ± 1.07 h (D = 40 mg) whereas that of anti-IIa ACT is shorter, fi) = 2.1 h). These results indicate that enoxaparin exhibits i) a differential anti-Xa/anti-IIa ACT profile, ii) a linear relationship between dose and anti-Xa/anti-IIa ACT and iii) a kinetic profile which is significantly different from that of standard heparin.

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.

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.

Chloramphenicol Pharmacokinetics in Infants and Young Children

PEDIATRICS ◽  
1980 ◽  
Vol 66 (4) ◽  
pp. 579-584
Author(s):  
Carolyn M. Sack ◽  
Jeffrey R. Koup ◽  
Arnold L. Smith
Keyword(s):  
Pediatric Patients ◽  
Total Body Clearance ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Wide Variability ◽  
Chloramphenicol Succinate ◽  
Total Body ◽  
Apparent Volume Of Distribution ◽  
Infants And Young Children ◽  
Body Clearance

We measured serum chloramphenicol concentrations in 17 hospitalized pediatric patients (aged 1 month to 6 years) after intravenous infusion of chloramphenicol succinate. The serum T½ ranged from 2.1 to 8.3 hours with a mean of 3.98 (SD 1.75) hours, while the apparent volume of distribution ranged from 0.78 to 2.09 liters/kg with a mean of 1.39 (SD 0.34) liters/kg. The total body clearance ranged 0.122 to 0.429 liters/kg/hour with a mean of 0.281 (SD 0.117) liters/kg/hour. Two patients were restudied, and had increased clearance during their hospitalization. Because of the wide variability in pharmacokinetics, we conclude that serum chloramphenicol concentrations should be monitored in infants and children.

The Pharmacokinetics of Buserelin after Intramuscular Administration in Pigs and Cows

2021 ◽  
Author(s):  
Zhengrong Gao ◽  
Yu Liu ◽  
Yuxin Yang ◽  
Yuying Cao ◽  
Jicheng Qiu ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Apparent Volume ◽  
Ultra Performance Liquid Chromatography ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Elimination Half ◽  
Liquid Chromatography Tandem Mass ◽  
Stability Method ◽  
Apparent Volume Of Distribution

Abstract Background: Buserelin is a LHRH agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not clearly understood. This study was designed to develop a sensitive method to determine the concentration of buserelin and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results: A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studies in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h·ng/mL for pigs and 5.63 ±1.86 h·ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ±0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2λz), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion: This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals.

Serum Quinidine Levels after Chronic Administration of Four Different Quinidine Formulations

1976 ◽  
Vol 4 (6) ◽  
pp. 393-401 ◽  
Author(s):  
A M Soeterboek ◽  
M Van Thiel
Keyword(s):  
Serum Level ◽  
Chronic Administration ◽  
Serum Levels ◽  
Relative Bioavailability ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Level Curves ◽  
Trough Serum ◽  
Total Body ◽  
Apparent Volume Of Distribution

The serum levels produced by four different quinidine formulations have been studied. The relative bioavailability of the formulations was demonstrated as were the mean peak serum levels and their timing in relation to dosage. From the data obtained, the biological half-lives were measured and the apparent volume of distribution and total body clearance were calculated for each formulation. The generic tablets of quinidine monosulphate from five different manufacturers were not significantly different from each other in any respect and produced the expected peak and trough serum level curves. The serum level curves resulting from administration of quinidine polygalacturonate (Cardioquin®) were not significantly different from those resulting from the generic tablets, and this formulation may be regarded as therapeutically equivalent to the generic formulations. Both sustained-release formulations of quinidine bisulphate, Durettes® and Kiditard® (given at the same dosage) were shown to offer a means whereby, with simple twice-daily dosage, quinidine maintenance treatment may be continued with the confidence that the serum levels may be maintained throughout each 24-hour period without peaks into the toxic levels and troughs into the levels of no effect.

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.

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