A COMPREHENSIVE QUANTITATIVE AND QUALITATIVE EVALUATION OF EXTRAPOLATION OF INTRAVENOUS PHARMACOKINETIC PARAMETERS FROM RAT, DOG, AND MONKEY TO HUMANS. II. VOLUME OF DISTRIBUTION AND MEAN RESIDENCE TIME

Objective: The present study was aimed to find out the effect of transdermal patches of proton pump inhibitors pantoprazole and esomeprazole on the alteration of pharmacokinetic parameters of these drugs. Methods: The transdermal patches were formulated by the solvent evaporation technique using polymers HPMC E5 with PVP K 30 and HPMC E5 with Eudragit L100 in different ratios. The best formulation from each of the drug pantoprazole and esomeprazole was selected and administered to rabbits and the plasma drug concentration was compared with the marketed formulation. The pharmacokinetic parameters such as maximum plasma concentration (Cmax), time to reach Cmax (tmax), area under the curve (AUC), area under first moment curve (AUMC), elimination rate constant (λz), biological half-life (t1/2), and mean residence time (MRT) were determined. Results: The plasma drug concentration vs time curve shows the extended-release of the drugs pantoprazole and esomeprazole when compared with the marketed formulation. The results show that there is no change in the peak plasma concentration, but a significant difference was observed in all the pharmacokinetic parameters. The AUC showed 6 fold increase for pantoprazole from 8.91 to 55.20 μg*h/ml and 3.5 fold increase for the drug esomeprazole from 7.86 to 28.53 μg*h/ml, and the mean residence time also showed 2 fold increase for the transdermal patches when compared with the marketed formulations. Conclusion: The increase in tmax, AUC, and MRT values of the formulated transdermal patches with the values of the marketed formulation of both the drugs, revealed that the transdermal patches can be used to deliver the drug for an extended period and also can alter the pharmacokinetics of pantoprazole and esomeprazole.

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Toxicokinetics of cotyledoside following intravenous administration to sheep

Journal of the South African Veterinary Association ◽

10.4102/jsava.v74i1.488 ◽

2003 ◽

Vol 74 (1) ◽

Cited By ~ 1

Author(s):

C.J. Botha ◽

T. Rundberget ◽

G.E. Swan ◽

M.S.G. Mulders ◽

A. Flaoyen

Keyword(s):

Single Dose ◽

Residence Time ◽

Mean Residence Time ◽

Cardiac Glycoside ◽

Compartmental Model ◽

Small Volume ◽

Volume Of Distribution ◽

Rapid Decline ◽

Time Intervals ◽

Rapid Clearance

Cotyledoside, a bufadienolide cardiac glycoside, was administered intravenously to sheep in 2 studies. In experiment 1, sheep (n = 4) received 0.0135 mg / kg daily on 5 consecutive days and in the 2nd experiment, sheep (n = 4) received 0.027 mg / kg as a single dose. Jugular blood was collected at different time intervals and kinetic parameters were determined. The data fitted a 1-compartmental model. In both experiments a short half-life (t1/2) and mean residence time (MRT), a relative small volume of distribution (Vdss) and rapid clearance were calculated. In the 1st experiment, t1/2 and MRT increased significantly (P < 0.007) from Day (D) 0 to D 4. It is suggested that the rapid decline in plasma cotyledoside concentrations in sheep denotes rapid distribution of cotyledoside to the tissues or extracellular spaces and possible accumulation at the biophase.

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Comparative Pharmacokinetic Study of Taxifolin after Oral Administration of Fructus Polygoni Orientalis Extract in Normal and Fibrotic Rats by UPLC-MS/MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9348075 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Feili Wei ◽

Li Guo ◽

Yongsong Xu ◽

Dexi Chen ◽

Muxin Gong

Keyword(s):

Liver Fibrosis ◽

Oral Administration ◽

Residence Time ◽

Mean Residence Time ◽

Internal Standard ◽

Rat Plasma ◽

Pharmacokinetic Parameters ◽

Porcine Serum ◽

Validation Parameters ◽

The Mean

Fructus polygoni orientalis (FPO) is widely used in clinical practice in China, especially in treatment of liver diseases including viral hepatitis, liver fibrosis, and liver cirrhosis. However, its pharmacokinetic (PK) alterations in liver fibrotic rats have rarely been reported. To study whether taxifolin, one of the main flavonoids in FPO can be absorbed into blood after oral administration of FPO extract and to compare the differences in pharmacokinetic parameters of taxifolin to normal and liver fibrotic rats induced by porcine serum (PS), a UPLC-MS/MS method was developed and validated for determination of taxifolin in rat plasma using puerarin as the internal standard (IS). All validation parameters met the acceptance criteria according to regulatory guidelines. The results indicated that after treatment of rats with PS alone for 12 weeks, the liver fibrotic model group was built successfully. The taxifolin can be absorbed into the blood after oral administration of the FPO extract. The Cmax of taxifolin was 1940 ± 502.2 ng/mL and 2648 ± 208.5 ng/mL (p<0.05), the AUC0∼t of taxifolin was 4949.7 ± 764.89 h·ng/mL and 6679.9 ± 734.26 h·ng/mL (p<0.05), the AUC0∼∞ of taxifolin was 5049.4 ± 760.7 and 7095.2 ± 962.3 h·ng/mL (p<0.05), and the mean residence time (MRT) of taxifolin was 2.46 ± 0.412 h and 3.17 ± 0.039 h (p<0.05) in the normal and fibrotic model groups, respectively. These results confirmed that the pharmacokinetic parameters of taxifolin are altered in liver fibrosis, manifested as Cmax, AUC0∼t, AUC0∼∞, and the mean residence time (MRT). It suggested that it is essential to consider the characteristics of pharmacokinetics after oral administration of FPO in liver disease patients.

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Dexmedetomidine Pharmacokinetics in Neonates with Hypoxic-Ischemic Encephalopathy Receiving Hypothermia

Anesthesiology Research and Practice ◽

10.1155/2020/2582965 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15 ◽

Cited By ~ 1

Author(s):

Ryan M. McAdams ◽

Daniel Pak ◽

Bojan Lalovic ◽

Brian Phillips ◽

Danny D. Shen

Keyword(s):

Steady State ◽

Residence Time ◽

Mean Residence Time ◽

Time Course ◽

Plasma Concentrations ◽

Distribution Volume ◽

Hypoxic Ischemic Encephalopathy ◽

Pharmacokinetic Parameters ◽

Open Label ◽

Ischemic Encephalopathy

Dexmedetomidine is a promising sedative and analgesic for newborns with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). Pharmacokinetics and safety of dexmedetomidine were evaluated in a phase I, single-center, open-label study to inform future trial strategies. We recruited 7 neonates ≥36 weeks’ gestational age diagnosed with moderate-to-severe HIE, who received a continuous dexmedetomidine infusion during TH and the 6 h rewarming period. Time course of plasma dexmedetomidine concentration was characterized by serial blood sampling during and after the 64.8 ± 6.9 hours of infusion. Noncompartmental analysis yielded descriptive pharmacokinetic estimates: plasma clearance of 0.760 ± 0.155 L/h/kg, steady-state distribution volume of 5.22 ± 2.62 L/kg, and mean residence time of 6.84 ± 3.20 h. Naive pooled and population analyses according to a one-compartment model provided similar estimates of clearance and distribution volume. Overall, clearance was either comparable or lower, distribution volume was larger, and mean residence time or elimination half-life was longer in cooled newborns with HIE compared to corresponding estimates previously reported for uncooled (normothermic) newborns without HIE at comparable gestational and postmenstrual ages. As a result, plasma concentrations in cooled newborns with HIE rose more slowly in the initial hours of infusion compared to predicted concentration-time profiles based on reported pharmacokinetic parameters in normothermic newborns without HIE, while similar steady-state levels were achieved. No acute adverse events were associated with dexmedetomidine treatment. While dexmedetomidine appeared safe for neonates with HIE during TH at infusion doses up to 0.4 μg/kg/h, a loading dose strategy may be needed to overcome the initial lag in rise of plasma dexmedetomidine concentration.

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Precipitation and filtration of zinc, magnesium, copper and aluminium hydroxides

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19823362 ◽

1982 ◽

Vol 47 (12) ◽

pp. 3362-3370

Author(s):

Otakar Söhnel ◽

Eva Matějčková

Keyword(s):

Residence Time ◽

Mean Residence Time ◽

Filtration Resistance ◽

Filtration Pressure ◽

Bed Porosity ◽

The Mean ◽

Filtration Properties

Filtration properties of batchwise precipitated suspensions of Zn(OH)2, Mg(OH)2 and Cu(OH)2 and continuously precipitated Al(OH)3 were studied. For batchwise precipitated suspensions was verified the theoretically predicted dependence of specific filtration resistance on initial supersaturation and for the continuously precipitated Al(OH)3 the relation between the specific filtration resistance and the mean residence time of suspension in the reactor. Dependences were also recorded between the bed porosity and concentration of precipitated solutions, specific filtration resistance and used filtration pressure and the effect of aging of the batchwise precipitated suspension of Mg(OH)2on its filtration properties. The used CST method for determination of filtration characteristics of Zn(OH)2 suspension was also studied.

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Nitrogen use efficiency: does a trade-off exist between the N productivity and the mean residence time within species?

Australian Journal of Botany ◽

10.1071/bt07139 ◽

2008 ◽

Vol 56 (3) ◽

pp. 272 ◽

Cited By ~ 11

Author(s):

Zhi Y. Yuan ◽

Han Y. H. Chen ◽

Ling H. Li

Keyword(s):

Residence Time ◽

Nitrogen Use Efficiency ◽

Mean Residence Time ◽

Negative Relationship ◽

Controlled Experiments ◽

Nitrogen Use ◽

Trade Off ◽

N Supply ◽

Use Efficiency ◽

The Mean

Nitrogen use efficiency (NUE) can be divided into two components, i.e. N productivity (A) and the mean residence time (MRT). Controlled experiments indicate that there is not a trade-off between A and MRT within species, but this theory has not been well tested in field conditions. Here, we studied the A, MRT and NUE of Stipa krylovii Roshev. in a grassland over 4 years of N fertilisation experimentation. The three parameters (A, MRT and NUE) were significantly related to soil N supply and there was a negative relationship between A and MRT within this species (r = –0.775, P < 0.05), i.e. plants with higher A had lower MRT. Our results showed a trade-off between A and MRT within this Stipa species and this observed trade-off was attributed to different responses of A and MRT to soil fertility.

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