Influence of hypercapnia and (or) hypoxemia and metabolic acidosis on sulfamethazine kinetics in the conscious rabbit

1984 ◽  
Vol 62 (9) ◽  
pp. 1170-1177 ◽  
Author(s):  
Patrick du Souich ◽  
Hélène Courteau
Keyword(s):  
Metabolic Acidosis ◽  
Protein Binding ◽  
Flow Distribution ◽  
Blood Gases ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Experimental Conditions ◽  
Multiple Blood ◽  
Total Body ◽  
Acute Changes

The aim of the present study was to determine whether acute changes in blood gases and pH alter sulfamethazine (SMZ) kinetics. Groups of conscious rabbits were exposed for 270 min either to air or to a high CO2 and (or) low O2 atmosphere to produce hypercapnia, hypoxemia, or both. Another group of rabbits received 47 mL/kg of 0.3 M HCl by gavage tube to induce metabolic acidosis. Once the blood gases were stabilized, the rabbits received 20 mg/kg SMZ i.v. Multiple blood samples were drawn for 180 min to assess SMZ kinetic parameters, SMZ protein binding, and blood gases. Fifteen minutes after the administration of SMZ, a suboccipital puncture was performed to determine the concentration of SMZ in the cerebrospinal fluid (CSF). Urine was collected for the first 180 min through a sterile catheter and for the next 21 h in a metabolic cage. Hypercapnia alone did not significantly influence SMZ kinetics. Hypoxemia, hypoxemia combined with hypercapnia, and metabolic acidosis increased the SMZ apparent volume of distribution (V) and total body clearance (CL). This increase in the SMZ V correlated positively (p < 0.01) to the ratio of SMZ concentration in CSF to SMZ concentration in plasma. The increase in SMZ CL was mainly due to an increase in nonrenal clearance, although a slight increase in SMZ renal clearance was also observed. Several factors may be related to these kinetic changes: (i) SMZ plasma protein binding decreased under these experimental conditions as a result of a decrease in the apparent intrinsic association constant; (ii) in addition, SMZ nonionized fraction may have increased by 42% in hypercapnia combined with hypoxemia and metabolic acidosis; (iii) theoretically, changes in blood flow distribution may have also contributed. It was concluded that the acute modification of blood gases and pH do influence SMZ kinetics, hypoxemia being the factor most responsible for kinetic changes.

scholarly journals Effects of Xuesaitong on the Pharmacokinetics of Losartan: An In Vivo UPLC-MS/MS Study

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Weina Ma ◽  
Lei Lv ◽  
Jungang Guo ◽  
Yongjun Meng ◽  
Yinghua Wang ◽  
...  
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Sprague Dawley ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Blood ◽  
Apparent Volume Of Distribution ◽  
Noncompartmental Model

The aim of this study was to examine whether Xuesaitong, a multiherbal formulation for coronary heart disease, alters the pharmacokinetics of losartan. Adult male Sprague Dawley rats randomly received losartan (10 mg/kg) or losartan plus Xuesaitong (10 mg/kg) through an oral gavage (n = 6). Multiple blood samples were obtained for up to 36 h to determine the concentrations of losartan and its active metabolite, EXP3174, through ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Pharmacokinetics were estimated using a noncompartmental model. The half-life (t1/2) of losartan was decreased by Xuesaitong (4.26 ± 1.51 vs. 6.35 ± 2.10 h; P<0.05). The apparent volume of distribution (Vd) of losartan was also decreased by the combination of losartan and Xuesaitong (4.41 ± 1.61 vs. 7.20 ± 2.41 mL; P<0.05). The time to maximum concentration (Tmax) of losartan was increased by Xuesaitong (1.06 ± 1.04 vs. 0.13 ± 0.05 h; P<0.05). Xuesaitong also decreased the t1/2 of EXP3174 (8.22 ± 1.41 vs. 6.29 ± 1.38 h; P<0.05). These results suggest that there is a complex interaction between losartan and Xuesaitong. In addition to enhanced elimination of losartan and EXP3174, Xuesaitong may also decrease the absorption rate and Vd of losartan.

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 Plasma pharmacokinetics of ciprofloxacin in sheep

1970 ◽  
Vol 6 (1) ◽  
pp. 93-97
Author(s):  
MS Islam ◽  
MMH Sikder ◽  
MA Awal ◽  
M Mostofa ◽  
AA Trisha
Keyword(s):  
Half Life ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Sheep Model ◽  
First Order Kinetics ◽  
Healthy Sheep ◽  
Plasma Pharmacokinetics ◽  
Total Body

The study was carried out to determine the biodisposition kinetics of ciprofloxacin in sheep model in Department of Pharmacology, Bangladesh Agricultural University. Healthy sheep of both sexes (n=65) were divided into 13 groups, each consists of five and given a single dose of ciprofloxacin @ 5 mg/kg bwt intramuscularly .Blood sample was collected from each group of sheep at 0, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10 and 12 hours interval respectively. Serum concentration of ciprofloxacin was determined by spectrophotometric method. The pharmacokinetic parameters were measured by single compartment open model and first order kinetics. The peak concentration of ciprofloxacin was 3.56±0.15mg/ ml, absorption half-life and biological half-life were 0.0846±1.79 and 1.75±0.15 h respectively. The apparent volume of distribution was found 35.54 mg/liter. The absorption rate constant was 8.188h-1, MRT was 2.647h-1 and total body clearances were found 16.88 h-1. These result suggested that a dose of 5 mg/kg bwt provides maximum plasma concentration and is effective in the control of many infectious diseases of sheep. Key words: Plasma pharmacokinetics, ciprofloxacin, sheep DOI = 10.3329/bjvm.v6i1.1344 Bangl. J. Vet. Med. (2008). 6 (1): 93-97

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.

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.

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.

Pharmacokinetics of PT523, a novel aminopterin analogue, in patients with solid tumors

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2052-2052
Author(s):  
J. G. Supko ◽  
X. He ◽  
N. Sao ◽  
F. D’Amato ◽  
L. Blaszkowsky ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Hepatic Function ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Entire Cohort ◽  
Median Plasma ◽  
Major Route ◽  
The Mean ◽  
Total Body ◽  
Log Linear

2052 Background: Nα-(4-Amino-4-deoxypteroyl)-N5-hemiphthaloyl)-L-ornithine (PT523) is a nonpolyglutamatable aminopterin analogue selected for clinical evaluation based upon properties that confer potential therapeutic advantages over classic and nonclassic antifolates. This report describes the pharmacokinetic (PK) behavior of PT523 in cancer patients as determined in the first phase I trial of the drug. Methods: Adult patients with refractory solid tumors received PT523 as a 5 min iv infusion every 7 days for 3 weeks. Plasma samples were obtained at -5, 4, 10, 15, 20, 30, 45 min; 1, 2, 3, 4, 6, 8, 24, and 48 h after starting the first weekly infusion. Urine was collected and pooled from 0–8, 8–24, and 24–48 h. An LC/MS assay was used to measure PT523 in plasma and urine. Interday accuracy and precision were both <15% at the lowest concentrations measured in plasma (0.50 ng/mL) and urine (50 ng/mL). PK parameters were estimated by standard noncompartmental methods. Results: The PK of PT523 was characterized in 24 patients with normal renal and hepatic function, and a median age of 52 years (range, 28 - 77 years). Data was obtained from groups of at least three patients receiving doses of 5, 6.7, 9, 12, and 16 mg/m2. The PT523 concentration in plasma decreased in a polyexponential manner and the terminal log-linear phase was achieved 4–6 h after dosing. In the 7 patients receiving doses of 16 mg/m2, the mean peak drug concentration in plasma (Cmax) was 5,650 ± 300 ng/mL and the median plasma concentration 48 h after dosing was 1.7 ng/mL (range, 1.0 - 23.4 ng/mL). The apparent biological half-life (t1/2,z), total body clearance (CL) and apparent volume of distribution at steady-state (Vss) were all independent of the dose. Mean ± SD values of PK parameters for the entire cohort of 24 patients were: CL, 1.16 ± 0.31 L/h/m2; t1/2,z, 5.3 ± 1.2 h; Vss, 7.7 ± 1.5 L/m2. The mean amount of the dose excreted as unchanged drug in urine over 48 h was 40 ± 15%. Conclusions: PT523 exhibits linear PK with moderate interpatient variability when administered as a 5 min iv infusion at doses of 5 - 16 mg/m2. Renal clearance is a major route of elimination. Association between the CL of PT523 and creatinine clearance should be evaluated in a future study to assess whether dose modification is warranted for patients with diminished renal function. No significant financial relationships to disclose.

scholarly journals Studies on effects of lactose on experimental Trypanosoma vivax infection in Zebu cattle. 1. Plasma kinetics of intravenously administered lactose at onset of infection and pathology

2008 ◽  
Vol 75 (2) ◽  
Author(s):  
M. Y. Fatihu ◽  
S. Adamu ◽  
I. A. Umar ◽  
N. D.G. Ibrahim ◽  
L. O. Eduvie ◽  
...  
Keyword(s):  
Muscular Atrophy ◽  
Elimination Rate ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Zebu Cattle ◽  
Trypanosoma Vivax ◽  
Histopathological Lesions ◽  
The Mean ◽  
Total Body

Lactose in normal saline was administered intravenously to a group of Zebu cattle infected with Trypanosoma vivax to determine the bloodplasma kinetics at onset of an experimental infection and its ability to protect tissues against damage as part of preliminary studies to determine its suitability for use in the treatment of trypanosomosis. Significant (P <0.01) higher lactose concentrations were observed in the T. vivax-intecled bulls at 30 min and 1h (P< 0.05) post-infectio (p.i.) and by 4 h p.i. the plasma lactose remained above the level prior to infusion, after which it fell slightly below the preinfusion level in the uninfected group. Calculated pharmacokinetic parameters revealed delayed excretion of lactose in the T. vivax-intected group soon after infection. The total body clearance (C/B )was significantly (P < 0.05) reduced. The biological half-life (t1/2), elimination rate constant (kel) and apparent volume of distribution (Vd) were relatively decreased (P > 0.05) as a result of the T. vivax infection. Retention of lactose in the plasma was attributed to decreased plasma clearance l.t is suggested that the presence of trypanosomes in circulation rather than organic lesions could have been responsible for the delay observed in the excretion of lactose.At 12 weeks p.i., when the experiment was terminated, the group infected and given lactose infusion (despiteh igherp arasitaemia) had no gross or histopathological lesions in the brain, spleen, lymphnodes, heart, kidneys, liver and testes. However, the group infected but not infused with lactose were emaciated, had pale mucosae, watery blood, general muscular atrophy, serous atrophy of coronary fat and other adiposet issue, hepatomegalys, plenomegalys, wollen and oedematous lymph nodes, all of which are suggestive of trypanosomosis. Histopathological lesions included arrowing of Bowman's space and hypercellularity of glomerular tufts in the kidneys with the mean glomerula truft nucleairn dices (GTNs) in the group significantly higher (P <0.01)than the mean GTNs of the lactoseinfused and control bulls. Degenerative changes occurred in the myocardium, spleen, testes and epididymides. The tesicular and epididymal lesions are indicative of male reproductive dysfunction.

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.

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