scholarly journals Pharmacokinetics and Bioequivalence Evaluation of Cyclobenzaprine Tablets

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Tatiane Maria de Lima Souza Brioschi ◽  
Simone Grigoleto Schramm ◽  
Eunice Kazue Kano ◽  
Eunice Emiko Mori Koono ◽  
Ting Hui Ching ◽  
...  
Keyword(s):  
Single Dose ◽  
Half Life ◽  
Healthy Subjects ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Open Model ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Overnight Fasting ◽  
Tablet Formulations

The purpose of this study was to investigate cyclobenzaprine pharmacokinetics and to evaluate bioequivalence between two different tablet formulations containing the drug. An open, randomized, crossover, single-dose, two-period, and two-sequence design was employed. Tablets were administered to 23 healthy subjects after an overnight fasting and blood samples were collected up to 240 hours after drug administration. Plasma cyclobenzaprine was quantified by means of an LC-MS/MS method. Pharmacokinetic parameters related to absorption, distribution, and elimination were calculated. Cyclobenzaprine plasma profiles for the reference and test products were similar, as well as absorption pharmacokinetic parameters AUC (reference: 199.4 ng∗h/mL; test: 201.6 ng∗h/mL), (reference: 7.0 ng/mL; test: 7.2 ng/mL), and (reference: 4.5 h; test: 4.6 h). Bioequivalence was evaluated by means of 90% confidence intervals for the ratio of AUC (93%–111%) and (93%–112%) values for test and reference products, which were within the 80%–125% interval proposed by FDA. Cyclobenzaprine pharmacokinetics can be described by a multicompartment open model with an average rapid elimination half-life () of 3.1 hours and an average terminal elimination half-life () of 31.9 hours.

Effect of the Addition of Ciprofloxacin on Theophylline Pharmacokinetics in Subjects Inhibited by Cimetidine

1992 ◽  
Vol 26 (1) ◽  
pp. 11-13 ◽  
Author(s):  
Robin L. Davis ◽  
Ronald W. Quenzer ◽  
H. William Kelly ◽  
J. Robert Powell
Keyword(s):  
Half Life ◽  
Repeated Measures ◽  
Enzyme Inhibitors ◽  
Enzyme Inhibitor ◽  
Combined Treatment ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Microsomal Enzyme ◽  
Elimination Half Life ◽  
Elimination Half

OBJECTIVE: Although the effect of individual enzyme inhibitors on hepatic microsomal enzyme activity has been studied extensively, little data exist on the effects of combinations of inhibiting agents. The purpose of this study was to investigate the effect of the addition of a second hepatic oxidative enzyme inhibitor on the inhibition of metabolism in subjects already maximally inhibited by cimetidine. Ciprofloxacin was used as the second inhibitor. DESIGN: In a randomized crossover sequence, subjects received theophylline 5 mg/kg on day 6 of therapy with cimetidine 2400 mg/d, ciprofloxacin 1 g/d, both drugs, or while drug-free. SETTING: National Institutes of Health-funded General Clinical Research Center. PARTICIPANTS: Eight normal volunteers (6 men, 2 women; mean age 25.2 y). OUTCOME MEASURES: Theophylline pharmacokinetic parameters after each treatment were determined by model independent pharmacokinetic analysis. Statistical analysis of the data for differences between treatments was assessed by ANOVA for repeated measures. RESEARCH: When administered alone, ciprofloxacin and cimetidine caused a significant increase in theophylline elimination half-life and a decrease in clearance. Theophylline elimination half-life was significantly longer during combined therapy compared with either drug alone. Theophylline clearance was lower during combined treatment, although this relationship did not reach statistical significance. CONCLUSIONS: The addition of a second enzyme inhibitor in subjects receiving maximally inhibiting doses of cimetidine can produce a further decrease in the hepatic metabolism of drugs that are metabolized by the cytochrome P-450 microsomal enzyme system. As cimetidine and ciprofloxacin are frequently used together for a variety of common clinical indications, clinicians should be aware of this drug interaction and should consider that a similar effect may occur when other enzyme inhibitors are used concomitantly.

Single Dose Pharmacokinetic Study of Lithium in Taiwanese/Chinese Bipolar Patients

1998 ◽  
Vol 32 (1) ◽  
pp. 133-136 ◽  
Author(s):  
Ching-Fa Lee ◽  
Yong-Yi Yang ◽  
Oliver Yoa-Pu Hu
Keyword(s):  
Single Dose ◽  
Racial Differences ◽  
Half Life ◽  
Lithium Carbonate ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Overnight Fasting ◽  
Ethnic Comparisons ◽  
Bipolar Patients ◽  
Kinetics Of

Objective: The purpose of this study is to investigate the single dose pharmaco-kinetics of lithium in Taiwanese/Chinese bipolar patients for future interracial comparisons. Method: Eight bipolar patients took 900 mg of lithium carbonate after overnight fasting. Blood samples of 5 mL were taken after 15 min, 30 min, 45 min, 1 h, 2 h, 3 h, 4 h, 7 h, 9 h, 15 h, 25 h and 31 h after dosing. The computer programs CSTRIP and PCNONLIN were used for pharmacokinetic analysis. Results: The pharmacokinetic parameters obtained were as follows: Cmax, 0.970 ± 0.170 (SD) mmoi/L; Tmax, 1.59 ± 0.78 h; AUC31h = 548.9 ± 135.4 mmol.m/L; AUC = 722.6 ± 262.7 mmol.m/L; β-half-life = 16.3 ± 7.18 h; K-half-life = 0.613 ± 0.442 h; CIoral = 1.13 ± 0.39 mL/min/kg; Vd/F = 1.43 ± 0.387 L/kg. Most of the pharmacokinetic parameters were within the ranges reported in investigations of Caucasian subjects. Conclusions: This study showed that racial differences in lithium pharmacokinetics might not exist. We suggest that methodological designs, including method of blood sampling, measurement of lithium, and pharmacokinetic and statistical calculations, be standardised if future cross-ethnic comparisons are to be conducted.

scholarly journals Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report

2021 ◽  
Vol 8 ◽  
Author(s):  
Joe S. Smith ◽  
Jonathan P. Mochel ◽  
Windy M. Soto-Gonzalez ◽  
Rebecca R. Rahn ◽  
Bryanna N. Fayne ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Half Life ◽  
Plasma Clearance ◽  
Primary Study ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Study Objective ◽  
Elimination Half Life ◽  
Elimination Half

Background: Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats.Objective: The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats.Methods: Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis.Results: Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 μg/mL, 0.8 h, and 0.2 hr*μg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study.Conclusion: The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.

Epidural, Cerebrospinal Fluid, and Plasma Pharmacokinetics of Epidural Opioids (Part 2)

2003 ◽  
Vol 99 (2) ◽  
pp. 466-475 ◽  
Author(s):  
Christopher M. Bernards ◽  
Danny D. Shen ◽  
Emily S. Sterling ◽  
Jason E. Adkins ◽  
Linda Risler ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Epidural Space ◽  
Drug Concentration ◽  
Half Life ◽  
Sampling Site ◽  
Pharmacokinetic Parameters ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Plasma Pharmacokinetics ◽  
Venous Plasma

Background The ability of epinephrine to improve the efficacy of epidurally administered drugs is assumed to result from local vasoconstriction and a consequent decrease in drug clearance. However, because drug concentration in the epidural space has never been measured, our understanding of the effect of epinephrine on epidural pharmacokinetics is incomplete. This study was designed to characterize the effect of epinephrine on the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids. Methods Morphine plus alfentanil, fentanyl, or sufentanil was administered epidurally with and without epinephrine (1:200,000) to pigs. Opioid concentration was subsequently measured in the epidural space, central venous plasma, and epidural venous plasma, and these data were used to calculate relevant pharmacokinetic parameters. Results The pharmacokinetic effects of epinephrine varied by opioid and by sampling site. For example, in the lumbar epidural space, epinephrine increased the mean residence time of morphine but decreased that of fentanyl and sufentanil. Epinephrine had no effect on the terminal elimination half-life of morphine in the epidural space, but it decreased that of fentanyl and sufentanil. In contrast, in the lumbar intrathecal space, epinephrine had no effect on the pharmacokinetics of alfentanil, fentanyl, or sufentanil, but it increased the area under the concentration-time curve of morphine and decreased its elimination half-life. Conclusions The findings indicate that the effects of epinephrine on the spinal pharmacokinetics of these opioids are complex and often antithetical across compartments and opioids. In addition, the data clearly indicate that the pharmacokinetic effects of epinephrine in spinal "compartments" cannot be predicted from measurements of drug concentration in plasma, as has been assumed for decades.

Single-Dose Pegfilgrastim after Chemotherapy Is Highly Effective in Enhancing the Mobilization of Autologous CD34+ Peripheral Blood Stem Cells in Patients with Lymphoid Malignancies and Solid Tumors.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2922-2922
Author(s):  
Frank Kroschinsky ◽  
Kristina Hoelig ◽  
Uwe Platzbecker ◽  
Eberhard Schleyer ◽  
Rainer Ordemann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Single Dose ◽  
Solid Tumors ◽  
Peripheral Blood ◽  
Half Life ◽  
Peripheral Blood Stem Cells ◽  
Elimination Half Life ◽  
Elimination Half ◽  
Cd34 Cells ◽  
Blood Stem Cells

Abstract The administration of myelosuppressive chemotherapy followed by daily injections of granulocyte-colony stimulating factor (G-CSF) is the common procedure to mobilize autologous CD34+ peripheral blood stem cells (PBPC). Pegfilgrastim (NeulastaTM, Amgen Inc., Thousand Oaks, USA) is a covalent conjugate of filgrastim and polyethylene glycol with an increased elimination half-life due to decreased serum clearance. Whereas a single injection of pegfilgrastim (PEGFIL) has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, the experiences with PEGFIL in mobilization of PBPC are limited. We report 40 pts (22 male, 18 female, median age 53 years) who had a PBPC mobilization treatment for Hodgkin′s lymphoma (n=3), non-Hodgkin′s lymphoma (n=13), multiple myeloma (n=16), acute lymphoblastic leukaemia (n=3) or solid tumors (n=5). The mobilization regimen consisted of disease specific chemotherapy and a single subcutaneous injection of 6 mg PEGFIL administered 48 hours after the end of cytotoxic treatment (day 0). CD34+ cells in the peripheral blood (PB-CD34) were measured if white blood cells (WBC) exceeded 1.0 Gpt/L after nadir. PBPC collections started at a PB-CD34 cell count >10/μl and were performed as large-volume apheresis (4x blood volume) using a Cobe Spectra (Gambro BCT Inc.). Additional conventional filgrastim (FIL) was given at a dose of 2x5μg/kg if PB-CD34 count was found to be <10/μl. Blood samples for pharmacokinetics were taken in 9 pts. The median start of aphereses was on day +9 after the administration of PEGFIL and on day +15 after start of chemotherapy regimen, respectively. Median PB-CD34 peak was 74/μl (range 9–565/μl). The median PBPC yield was 7.6 x 10^6 CD34+ cells/kg (range 1.5–88.1). The target cell dose to be collected (≥ 2.5 x 10^6 CD34+ cells/kg) was achieved in 36 (90 %) pts, in 29 pts (72.5 %) ≥ 4.0 x 10^6 CD34+ cells/kg could be obtained with a single collection. Additional FIL administrations were necessary in 7 patients (17.5 %) for 2 to 6 days. All of them were heavily pretreated including a previous autologous transplant in two of these patients. PEGFIL was well tolerated except for moderate bone pain which occurred in all patients. The mean values (± SD) for peak plasma concentration of PEGFIL (cmax), time to reach the maximum plasma level (tmax) and elimination half-life (t1/2) were 154 (± 83) ng/ml, 56 (±21) hours and 23 (± 9) hours, respectively. We conclude that a single dose of 6 mg PEGFIL after chemotherapy is safe and highly effective in enhancing the mobilization of CD34+ PBPC for stem cell collection. Further investigations are warranted, including comparison with non-pegylated G-CSFs and in combination with antiadhesive agents.

scholarly journals Azelastine and suplatast shorten the distribution half-life of IgE in rats

2002 ◽  
Vol 11 (1) ◽  
pp. 61-64 ◽  
Author(s):  
Kazuhiko Hanashiro ◽  
Yoshihiro Tokeshi ◽  
Toshiyuki Nakasone ◽  
Masanori Sunagawa ◽  
Mariko Nakamura ◽  
...  
Keyword(s):  
Immunosorbent Assay ◽  
Rate Constants ◽  
Half Life ◽  
Wistar Rats ◽  
Immunoglobulin E ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Distilled Water ◽  
Elimination Half Life ◽  
Elimination Half

We aim to clarify whether suplatast and azelastine (anti-allergic drugs) can shorten the half-life of immunoglobulin E (IgE) in the circulating blood. Thirty Wistar rats were divided into six groups. Distilled water or anti-allergic drugs were given orally for 6 days after the first sensitization. Two milligrams of monoclonal dinitrophenyl (DNP)-specific rat IgE was administered to the rats, which had been given suplatast or azelastine orally. The level of DNP-specific rat IgE in the serum was estimated by IgE-capture enzyme-linked immunosorbent assay, and the turnover of IgE was analyzed from its pharmacokinetic parameters. The elimination half-life of rat IgE was about 12 h irrespective of the sensitized state. The intercompartmental rate constants (KctandKtc) in the suplatast-administered or azelastine-administered group were larger than those of the distilled water-administered group under non-sensitized conditions. These findings suggested that the anti-allergic drugs used in the present study facilitated the excretion of IgE from the circulation in rats.

Measured Context-sensitive Half-times of Remifentanil and Alfentanil

1995 ◽  
Vol 83 (5) ◽  
pp. 968-975 ◽  
Author(s):  
Atul Kapila ◽  
Peter S. A. Glass ◽  
James R. Jacobs ◽  
Keith T. Muir ◽  
David J. Hermann ◽  
...  
Keyword(s):  
Drug Concentration ◽  
Half Life ◽  
Computer Modelling ◽  
Constant Infusion ◽  
Pharmacokinetic Parameters ◽  
Half Time ◽  
Elimination Half Life ◽  
Context Sensitive ◽  
Elimination Half ◽  
True Time

Abstract Background The context-sensitive half-time, rather than the terminal elimination half-life, has been proposed as a more clinically relevant measure of decreasing drug concentration after a constant infusion of a given duration. The context-sensitive half-time is derived from computer modelling using known pharmacokinetic parameters. The modelled context-sensitive half-time for a 3-h infusion of alfentanil is 50–55 min and is 3 min for remifentanil. The terminal elimination half-life is 111 min for alfentanil and 12–30 min for remifentanil. It has not been tested whether the modelled context-sensitive half-time reflects the true time for a 50% decrease in drug concentration or drug effect.

scholarly journals Effects of delivery via pressure-adjustable pneumatic gas-powered dart gun of three antimicrobial drugs (ceftiofur crystalline free acid, tildopirosin, and tulathromycin) on drug disposition and meat quality in cattle

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11822
Author(s):  
Thomas B. Hairgrove ◽  
Virginia Fajt ◽  
Ronald Gill ◽  
Rhonda Miller ◽  
Michael Miller ◽  
...  
Keyword(s):  
Half Life ◽  
Drug Disposition ◽  
Free Acid ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Carcass Quality ◽  
Antimicrobial Drugs ◽  
Elimination Half Life ◽  
Routes Of Administration ◽  
Elimination Half

Background Although Beef Quality Assurance guidelines do not recommend use of darting methods to deliver drugs, cattle in the US may be raised on farms and ranches without restraint facilities, and reports from the field suggest that dart guns are being used to deliver antimicrobial drugs. Few studies report whether this route of administration results in altered drug disposition or carcass quality. Methods Forty steers were blocked by sire and then randomly assigned to treatment with saline, ceftiofur crystalline free acid, tildipirosin, or tulathromycin delivered via dart gun. To assess drug disposition, eight ceftiofur, six tulathromycin, and six tildipirosin-treated calves were selected to measure plasma concentrations of drugs up to 10 days after drug administration. Steers were then fed a balanced ration for approximately 6.5 months and slaughtered. To evaluate carcass quality, tenderness of steaks from darted-side and non-darted sides was evaluated via Warner–Bratzler shear force testing. Due to the prohibition of extralabel routes of administration for ceftiofur in the U.S., animals treated with this drug did not enter the food supply. Results Ceftiofur disposition differed from published reports with lower mean Cmax but similar mean apparent elimination half-life. Tildipirosin disposition differed from published reports with lower Cmax and shorter apparent elimination half-life. Tulathromycin was similar to previous published reports but Cmax and apparent elimination half-life was highly variable. All steaks (from darted and non-darted sides) from cattle treated with ceftiofur and saline were more tender than from cattle treated with tulathromycin or tildipirosin (P = 0.003). There was a trend toward more tenderness in steaks from the non-darted compared to the darted side. Steaks from the darted side for one treatment, tildipirosin, were less tender than the non-darted side. Conclusions Pharmacokinetic parameters of ceftiofur crystalline free acid, tildipirosin, and tulathromycin to cattle using pressure-adjustable pneumatic gas-powered dart gun were estimated in this study. Delivery of tildipirosin and tulathromycin to cattle with dart gun may also result in detectable decreases in tenderness of harvested steaks.

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