Doxorubicin and doxorubicinol: intra-and inter-individual variations of pharmacokinetic parameters

1990 ◽  
Vol 27 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Jeanne-Marie Jacquet ◽  
Fran�oise Bressolle ◽  
Marc Galtier ◽  
Magali Bourrier ◽  
Daniel Donadio ◽  
...  
Keyword(s):  
Pharmacokinetic Parameters ◽  
Individual Variations

Large Intra-subject Variability in Caffeine Pharmacokinetics: Randomized Cross-over Study of Single Caffeine Product

Drug Research ◽  
2017 ◽  
Vol 67 (09) ◽  
pp. 539-546 ◽  
Author(s):  
Muhammad Hammami ◽  
Syed Alvi
Keyword(s):  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Absolute Deviation ◽  
Measured Concentration ◽  
Average Bioequivalence ◽  
Concentration Time ◽  
Individual Variations ◽  
Subject Variability ◽  
Bioequivalence Range ◽  
First Time

Abstract Background Average bioequivalence has been criticized for not adequately addressing individual variations. Importance of subjects’ blinding in bioequivalence studies has not been well studied. We explored the extent of intra-subject pharmacokinetic variability and effect of drug-ingestion unawareness in subjects taking single caffeine product. Methods A single-dose randomized cross-over design was used to compare pharmacokinetics of 200 mg caffeine, described as caffeine (overt) or as placebo (covert). Maximum concentration (Cmax), Cmax first time (Tmax), area-under-the-concentration-time-curve, to last measured concentration (AUCT), extrapolated to infinity (AUCI), or to Tmax of overt caffeine (AUCOverttmax), and Cmax/AUCI were calculated blindly using standard non-compartmental method. Percentages of individual covert/overt ratios that are outside the ±25% range were determined. Covert-vs-overt effect on caffeine pharmacokinetics was evaluated by 90% confidence interval (CI) and 80.00–125.00% bioequivalence range. Results 32 healthy subjects (6% females, mean (SD) age 33.3 (7.2) year) participated in the study (28 analysed). Out of the 28 individual covert/overt ratios, 23% were outside the ±25% range for AUCT, 30% for AUCI, 20% for AUCOverttmax, 30% for Cmax, and 43% for Tmax. There was no significant covert-vs-overt difference in any of the pharmacokinetic parameters studied. Further, the 90% CIs for AUCT, AUCI, Cmax, AUCOverttmax, and Cmax/AUCI were all within the 80.00–125.00% bioequivalence range with mean absolute deviation of covert/overt ratios of 3.31%, 6.29%, 1.43%, 1.87%, and 5.19%, respectively. Conclusions Large intra-subject variability in main caffeine pharmacokinetic parameters was noted when comparing an oral caffeine product to itself. Subjects’ blinding may not be important in average bioequivalence studies.

INTER-INDIVIDUAL PHARMACOKINETIC VARIATIONS AFTER INTRAVENOUS (IV) AND SUBCUTANEOUS (SC) INJECTION OF CY 216 IN HEALTHY SUBJECTS

1987 ◽  
Author(s):  
B Boneu ◽  
G Houin ◽  
M Rostin ◽  
J L Montastructure ◽  
P d’Azemar ◽  
...  
Keyword(s):  
Half Life ◽  
Ex Vivo ◽  
Clinical Results ◽  
Distribution Volume ◽  
Pharmacokinetic Parameters ◽  
Close Monitoring ◽  
Pharmacological Effects ◽  
Factor X ◽  
Individual Variations

We investigated the pharmacokinetic parameters and their inter individual variations of a low molecular weight heparin (LMWH) derivative (CY 216, Fraxiparine R, Choay). In a cross-over study, 100 anti Xa IC u/kg were injected in 12 healthy volunteers, either by IV or SC route, at one week interval. The pharmacological effects were followed on 12 serial citrated samples for 24h: - anti factor Xa (AXa) activity (chromogenic assay calibrated against CY 216); - APTT and thrombin clotting time prolongation. The main pharmacokinetic parameters (elimination half-life (T|); clearance (cl); distribution volume (Vd); bioavailability F (SC/ IV)) were calculated from the anti Xa activity curves using con-, ventional methods. The results (mean, range) indicated below confirm some classical properties of CY 216: poor anticoagulant effect (APTT-TT), even after IV injection, longer half-life than . standard Heparin (SH), distribution volume similar to plasma volume, excellent bioavailability of the drug.We also emphasize important inter-individual variations between volunteers, as known for the pharmacological effects of SH in vitro and ex-vivo. From those results it could be assumed that, as for SH, close monitoring of treatment with LMWH would be suitable with higher dosages, after validation of the correlations between those biological tests and clinical results.* anti Xa IC u : anti factor X activated Institut Choay unit.

Prosodic Impairment Associated With Traumatic Brain Injury

2009 ◽  
Vol 19 (3) ◽  
pp. 97-102
Author(s):  
Billy Irwin
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Detailed Analysis ◽  
Acoustic Characteristics ◽  
Individual Variations

Abstract Purpose: This article discusses impaired prosody production subsequent to traumatic brain injury (TBI). Prosody may affect naturalness and intelligibility of speech significantly, often for the long term, and TBI may result in a variety of impairments. Method: Intonation, rate, and stress production are discussed in terms of the perceptual, physiological, and acoustic characteristics associated with TBI. Results and Conclusions: All aspects of prosodic production are susceptible to the effects of damage resulting from TBI. There are commonly associated prosodic impairments; however, individual variations in specific aspects of prosody require detailed analysis.

Determination of Radiochemical Purity and Pharmacokinetic Parameters of 99mTc-Sulphur Colloid and 99mTc-Tin Colloid

1981 ◽  
Vol 20 (06) ◽  
pp. 279-282 ◽  
Author(s):  
D. Konstantinovska ◽  
K. Milivojević ◽  
J. Bzenić ◽  
V. Jovanović
Keyword(s):  
Radiochemical Purity ◽  
Slow Component ◽  
Pharmacokinetic Parameters ◽  
Optimum Size ◽  
Buffer Solution ◽  
Chromatography Method ◽  
Fast Phase ◽  
Biodistribution Studies ◽  
Biological Half Time

Labelling yield and radiochemical purity, higher than 95%, of 99mTc-colloid preparations were determined by using the paper chromatography method. Less than 3% of labelled citric acid, added to the preparation as a buffer solution, has been found in 99mTc-sulphur colloid. High radiochemical purity and optimum size of colloid particles has also been proved by biodistribution studies on experimental animals. The analysis performed has shown that more than 50% of 99mTc-colloid preparations excreted by urine is 99mTcO–, the remaining past 50% being protein bound 99mTc. Biological half-time of excretion of the fast phase is the same for both preparations, i.e. 10 min, while for the slow component it is 120 min in 99mTc-S-colloid and 160 min in 99mTc-Sn colloid.

Structured Data Entry for Reliable Acquisition of Pharmacokinetic Data

1996 ◽  
Vol 35 (03) ◽  
pp. 261-264 ◽  
Author(s):  
T. Schromm ◽  
T. Frankewitsch ◽  
M. Giehl ◽  
F. Keller ◽  
D. Zellner
Keyword(s):  
Text Processing ◽  
Data Entry ◽  
Processing System ◽  
Database System ◽  
Structured Data ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Probability Of Error ◽  
Error Frequency ◽  
Estimated Error

Abstract:A pharmacokinetic database was constructed that is as free of errors as possible. Pharmacokinetic parameters were derived from the literature using a text-processing system and a database system. A random data sample from each system was compared with the original literature. The estimated error frequencies using statistical methods differed significantly between the two systems. The estimated error frequency in the text-processing system was 7.2%, that in the database system 2.7%. Compared with the original values in the literature, the estimated probability of error for identical pharmacokinetic parameters recorded in both systems is 2.4% and is not significantly different from the error frequency in the database. Parallel data entry with a text-processing system and a database system is, therefore, not significantly better than structured data entry for reducing the error frequency.

Predicting Daily Maintenance Dose of Fluindione, an Oral Anticoagulant Drug

1996 ◽  
Vol 75 (05) ◽  
pp. 731-733 ◽  
Author(s):  
V Cazaux ◽  
B Gauthier ◽  
A Elias ◽  
D Lefebvre ◽  
J Tredez ◽  
...  
Keyword(s):  
Effective Dose ◽  
Maintenance Dose ◽  
Successive Approximations ◽  
Hemorrhagic Complication ◽  
Simple Method ◽  
Individual Variations ◽  
Anticoagulant Drug ◽  
The Mean ◽  
Mean Time ◽  
Daily Maintenance Dose

SummaryDue to large inter-individual variations, the dose of vitamin K antagonist required to target the desired hypocoagulability is hardly predictible for a given patient, and the time needed to reach therapeutic equilibrium may be excessively long. This work reports on a simple method for predicting the daily maintenance dose of fluindione after the third intake. In a first step, 37 patients were delivered 20 mg of fluindione once a day, at 6 p.m. for 3 consecutive days. On the morning of the 4th day an INR was performed. During the following days the dose was adjusted to target an INR between 2 and 3. There was a good correlation (r = 0.83, p<0.001) between the INR performed on the morning of day 4 and the daily maintenance dose determined later by successive approximations. This allowed us to write a decisional algorithm to predict the effective maintenance dose of fluindione from the INR performed on day 4. The usefulness and the safety of this approach was tested in a second prospective study on 46 patients receiving fluindione according to the same initial scheme. The predicted dose was compared to the effective dose soon after having reached the equilibrium, then 30 and 90 days after. To within 5 mg (one quarter of a tablet), the predicted dose was the effective dose in 98%, 86% and 81% of the patients at the 3 times respectively. The mean time needed to reach the therapeutic equilibrium was reduced from 13 days in the first study to 6 days in the second study. No hemorrhagic complication occurred. Thus the strategy formerly developed to predict the daily maintenance dose of warfarin from the prothrombin time ratio or the thrombotest performed 3 days after starting the treatment may also be applied to fluindione and the INR measurement.

A Multicenter Study of Recombinant Factor VIII (RecombinateTM) in Previously Treated Patients with Hemophilia A

1997 ◽  
Vol 77 (04) ◽  
pp. 660-667 ◽  
Author(s):  
G C White ◽  
S Courter ◽  
G L Bray ◽  
M Lee ◽  
E D Gomperts ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Recombinant Dna ◽  
Home Treatment ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Open Label ◽  
Treat Ment ◽  
Previously Treated Patients ◽  
Bleeding Episodes

SummaryA prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treat- ment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII; none was serious. No patient developed an inhibitor to r FVIII.

Sign in / Sign up

Export Citation Format

Share Document