Pharmacokinetic Analysis of Maprotiline and Its Demethylated Metabolite in Serum and Brain of Rats after Acute and Chronic Oral Administration of Maprotiline

1992 ◽  
Vol 81 (10) ◽  
pp. 1032-1037
Author(s):  
Katsushi Miyake ◽  
Hiroshi Fukuchi ◽  
Teruaki Kitaura ◽  
Masahiko Kimura ◽  
Yasuhiro Kimura
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Analysis

Pharmacokinetic analysis of orally administered puerarin in human saliva using an indirect competition ELISA

2015 ◽  
Vol 7 (19) ◽  
pp. 8335-8343 ◽  
Author(s):  
Qu Huihua ◽  
Wan Feng ◽  
Shan Wenchao ◽  
Wang Xueqian ◽  
Cheng Jinjun ◽  
...  
Keyword(s):  
Oral Administration ◽  
Human Saliva ◽  
Pharmacokinetic Analysis ◽  
Competition Elisa

The pharmacokinetics of puerarin in human saliva following oral administration of pueraria capsules were successfully studied by an icELISA method.

scholarly journals Oral Administration of Zolpidem Tartrate in an Abuse-deterrent Formulation Versus an Immediate Release Formulation in Beagle Dogs

2021 ◽  
pp. 1-6
Author(s):  
Amina Vazda ◽  
Wei Xia ◽  
Håkan Engqvist
Keyword(s):  
Controlled Release ◽  
Oral Administration ◽  
Chemical Properties ◽  
Immediate Release ◽  
Prescription Drug Abuse ◽  
Pharmacokinetic Analysis ◽  
Beagle Dogs ◽  
Release Formulation ◽  
Physical And Chemical ◽  
Plasma Profile

Objective: The continuing rise of prescription drug abuse has greatly necessitated the development of an abuse-deterrent formulation. Geopolymers are a promising base for drug design as they allow for tuneable drug release and possess superior physical and chemical properties compared with conventional pharmaceutical excipients.Methods: Geopolymer pellets containing zolpidem tartrate were administrated orally to beagle dogs as a controlled-release formulation with the commercial immediate-release product, Stilnoct® tablets, as the control.Results: The administration of zolpidem tartrate as immediate-release tablets demonstrated an elevated immediate release plasma profile and the zolpidem tartrate in the geopolymers demonstrated a controlled-release plasma profile. The pharmacokinetic analysis demonstrated that immediate-release tablet administration generated much higher plasma concentration when compared with geopolymer pellets administration for zolpidem tartrate. On the other hand, the geopolymer formulation prolonged the time of drug release.Conclusion: Oral administration of zolpidem tartrate in geopolymer pellets demonstrated a controlled-release plasma profile.

scholarly journals Modeling the Autoinhibition of Clarithromycin Metabolism during Repeated Oral Administration

2009 ◽  
Vol 53 (7) ◽  
pp. 2892-2901 ◽  
Author(s):  
Khaled Abduljalil ◽  
Martina Kinzig ◽  
Jürgen Bulitta ◽  
Stefan Horkovics-Kovats ◽  
Fritz Sörgel ◽  
...  
Keyword(s):  
Oral Administration ◽  
Time Course ◽  
Standard Dose ◽  
Model Development ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Weibull Function ◽  
Time Profiles

ABSTRACT Clarithromycin decreases CYP3A4 activity and thus gradually inhibits its own metabolism as well as that of coadministered drugs. The aim of this study was to obtain an understanding of the time course of these changes. The plasma concentration-time profiles of clarithromycin and its active metabolite, 14(R)-hydroxy-clarithromycin, in 12 young healthy volunteers after oral administration of a clarithromycin suspension (500 mg twice a day [b.i.d.] for seven doses) were modeled by population pharmacokinetic analysis in the NONMEM program. The nonlinearity of clarithromycin metabolism was considered during model development, and the metabolite disposition kinetics were assumed to be linear. The absorption kinetics of clarithromycin were best described by a Weibull function model. The pharmacokinetics of clarithromycin and its 14(R)-hydroxyl metabolite were adequately described by a one-compartment model each for clarithromycin and its metabolite as well as an inhibition compartment that reflects the autoinhibition of clarithromycin metabolism. Up to 90% of the apparent total clarithromycin clearance (60 liters/h) was susceptible to reversible autoinhibition, depending on the concentration in the inhibition compartment. The proposed semimechanistic population pharmacokinetic model successfully described the autoinhibition of clarithromycin metabolism and may be used to adjust the doses of other drugs that are metabolized by CYP3A4 and that are coadministered with clarithromycin. Simulations showed that for the standard dose of 500 mg b.i.d., no further increase in the level of exposure occurs after approximately 48 h of treatment. For a 1,000-mg b.i.d. dose, the achievement of steady state is expected to take several days and to achieve a 3.6-fold higher level of clarithromycin exposure than the 500-mg b.i.d. dose. This evaluation provides a rationale for safer and more effective therapy with clarithromycin.

scholarly journals An FtsZ-Targeting Prodrug with Oral Antistaphylococcal EfficacyIn Vivo

2013 ◽  
Vol 57 (12) ◽  
pp. 5860-5869 ◽  
Author(s):  
Malvika Kaul ◽  
Lilly Mark ◽  
Yongzheng Zhang ◽  
Ajit K. Parhi ◽  
Edmond J. LaVoie ◽  
...  
Keyword(s):  
Oral Administration ◽  
Mannich Base ◽  
Pharmacokinetic Analysis ◽  
Infection Model ◽  
Bacterial Cell Division ◽  
Content Type ◽  
Cytotoxicity Studies ◽  
Antistaphylococcal Activity ◽  
Base Derivative

ABSTRACTThe bacterial cell division protein FtsZ represents a novel antibiotic target that has yet to be exploited clinically. The benzamide PC190723 was among the first FtsZ-targeting compounds to exhibitin vivoefficacy in a murine infection model system. Despite its initial promise, the poor formulation properties of the compound have limited its potential for clinical development. We describe here the development of anN-Mannich base derivative of PC190723 with enhanced drug-like properties and oralin vivoefficacy. TheN-Mannich base derivative (TXY436) is ∼100-fold more soluble than PC190723 in an acidic aqueous vehicle (10 mM citrate, pH 2.6) suitable for oralin vivoadministration. At physiological pH (7.4), TXY436 acts as a prodrug, converting to PC190723 with a conversion half-life of 18.2 ± 1.6 min. Pharmacokinetic analysis following intravenous administration of TXY436 into mice yielded elimination half-lives of 0.26 and 0.96 h for the TXY436 prodrug and its PC190723 product, respectively. In addition, TXY436 was found to be orally bioavailable and associated with significant extravascular distribution. Using a mouse model of systemic infection with methicillin-sensitiveStaphylococcus aureusor methicillin-resistantS. aureus, we show that TXY436 is efficaciousin vivoupon oral administration. In contrast, the oral administration of PC190723 was not efficacious. Mammalian cytotoxicity studies of TXY436 using Vero cells revealed an absence of toxicity up to compound concentrations at least 64 times greater than those associated with antistaphylococcal activity. These collective properties make TXY436 a worthy candidate for further investigation as a clinically useful agent for the treatment of staphylococcal infections.

Pharmacokinetic Analysis of Two Different Doses of Duloxetine Following Oral Administration in Dogs

Drug Research ◽  
2013 ◽  
Vol 63 (08) ◽  
pp. 404-408 ◽  
Author(s):  
I.-H. Baek ◽  
B.-Y. Lee ◽  
W. Kang ◽  
K.-I. Kwon
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Analysis ◽  
Different Doses

scholarly journals Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 71 ◽  
Author(s):  
Yu-Feng Yao ◽  
Chao-Zhan Lin ◽  
Fang-Le Liu ◽  
Run-Jing Zhang ◽  
Qiu-Yu Zhang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Degradation Products ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Studies ◽  
Maximum Plasma ◽  
Time Curve ◽  
Tof Ms

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites—rhamnocitrin 3-O-β-glc and rhamnocitrin—in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites—rhamnocitrin—was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

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