A Comparison of the Pharmacokinetics and Tolerability of the Anti-Migraine Compound Almotriptan in Healthy Adolescents and Adults

Cephalalgia ◽  
2004 ◽  
Vol 24 (4) ◽  
pp. 288-292 ◽  
Author(s):  
JR Baldwin ◽  
JC Fleishaker ◽  
NE Azie ◽  
BJ Carel
Keyword(s):  
High Performance ◽  
Age Groups ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Lower Body ◽  
Compartment Analysis ◽  
Lower Body Weight ◽  
Adolescents And Adults ◽  
Two Populations ◽  
Two Age Groups

This study was designed to assess and compare the pharmacokinetics and tolerability of almotriptan, a 5-HT1B/1D agonist used to treat migraine attacks, in adolescents and adults. Healthy adolescents ( n = 18) and adults ( n = 18) received a single 12.5-mg dose of almotriptan after fasting overnight. Plasma and urinary almotriptan concentrations were measured by high-performance liquid chromatography. Pharmacokinetic parameters of almotriptan were determined by non-compartment analysis. The 90% confidence interval (CI) approach was employed to assess age effects. Mean Cmax, tmax, area under the curve (AUC 0-∞), half-life, and percentage excreted in urine were nearly identical for the two populations. Mean oral (CLPO) and renal (CLR) clearances were similar between the age groups; however, weight-corrected CLPO was approximately 32% higher (90% CI 16, 51) in adolescents compared with adults. The higher weight-corrected CLPO appeared to offset increases in exposure expected on the basis of lower body weight in adolescents. The findings were the same when a subgroup ( n = 9) of 12-14-year old children was compared with adults. The type, incidence and severity of adverse events were similar between the two age groups and were consistent with those reported previously during adult clinical trials. Based on these pharmacokinetic and tolerability findings, no dose adjustment for almotriptan would be required when treating patients as young as 12 years old.

Comparative Pharmacokinetic of Three Sulfadiazine Suspensions by Oral Administration in Chickens

2016 ◽  
Vol 8 (2) ◽  
pp. 122
Author(s):  
Zhi-Qiang Wang ◽  
Han-Song Li ◽  
Xia Xiao ◽  
Jian-Bing Wang
Keyword(s):  
Plasma Concentration ◽  
Broiler Chickens ◽  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Peak Time ◽  
Comparative Pharmacokinetic ◽  
Elimination Half ◽  
Maximal Plasma

<p>The chemotherapeutics, sulfadiazine (SDA) and trimethoprim (TMP), are extensively used in a variety of animal species. In this study, a pharmacokinetic analysis was performed to compare the bioequivalence of a combined SDA and TMP product against existing licensed SDA and TMP formulations in broiler chickens. Three groups of 15 birds were administered a single dose of either the test formulation or a reference oral suspension. The plasma concentration of SDA and TMP were determined by reverse-phase high performance liquid chromatography (HPLC), and the maximal plasma concentration (C<sub>max</sub>), area under the curve (AUC), the peak time (T<sub>max</sub>), mean residence time (MRT) and elimination half-life (T<sub>1/2</sub>), were calculated for SDA. The combined formulation I and II reference suspension exhibited almost identical concentration-time curves, and ANOVA analyses of the pharmacokinetic parameters identified no significant differences between the reference preparations and the test one. Furthermore the AUC and C<sub>max</sub> values of the SDA active ingredient were not significantly different. The I formulation was bioequivalent with both II and III (80-125% and 70–143%, respectively, at the 90% confidence interval). In conclusion, the combined SDA and TMP product was bioequivalent with both existing commercially available SDA suspensions and can be used interchangeably in veterinary medical practice.</p>

scholarly journals Compartmental Pharmacokinetics of the Antifungal Echinocandin Caspofungin (MK-0991) in Rabbits

2001 ◽  
Vol 45 (2) ◽  
pp. 596-600 ◽  
Author(s):  
Andreas H. Groll ◽  
Bryan M. Gullick ◽  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Myrna Candelario ◽  
...  
Keyword(s):  
High Performance ◽  
Pharmacokinetic Model ◽  
Area Under The Curve ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Chromatography Method ◽  
Opportunistic Fungi ◽  
The Mean ◽  
Liquid Chromatography Method

ABSTRACT The pharmacokinetics of the antifungal echinocandin-lipopeptide caspofungin (MK-0991) in plasma were studied in groups of three healthy rabbits after single and multiple daily intravenous administration of doses of 1, 3, and 6 mg/kg of body weight. Concentrations were measured by a validated high-performance liquid chromatography method and fitted into a three-compartment open pharmacokinetic model. Across the investigated dosage range, caspofungin displayed dose-independent pharmacokinetics. Following administration over 7 days, the mean peak concentration in plasma (C max) ± standard error of the mean increased from 16.01 ± 0.61 μg/ml at the 1-mg/kg dose to 105.52 ± 8.92 μg/ml at the 6-mg/kg dose; the mean area under the curve from 0 h to infinity rose from 13.15 ± 2.37 to 158.43 ± 15.58 μg · h/ml, respectively. The mean apparent volume of distribution at steady state (Vdss) was 0.299 ± 0.011 liter/kg at the 1-mg/kg dose and 0.351 ± 0.016 liter/kg at the 6-mg/kg dose (not significant [NS]). Clearance (CL) ranged from 0.086 ± 0.017 liter/kg/h at the 1-mg/kg dose to 0.043 ± 0.004 liter/kg/h at the 6-mg/kg dose (NS), and the mean terminal half-life was between 30 and 34 h (NS). Except for a trend towards an increasedVdss, there were no significant differences in pharmacokinetic parameters in comparison to those after single-dose administration. Caspofungin was well tolerated, displayed linear pharmacokinetics that fit into a three-compartment pharmacokinetic model, and achieved sustained concentrations in plasma that were multiple times in excess of reported MICs for susceptible opportunistic fungi.

Exposure to chloroquine in male adults and children aged 9–11 years with malaria due to Plasmodium vivax

2020 ◽  
Author(s):  
Michelle Valeria Dias Ferreira Vieira ◽  
José Luiz Fernandes Vieira
Keyword(s):  
Plasmodium Vivax ◽  
High Performance ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Time Profile ◽  
Pharmacokinetic Parameters ◽  
Older Children ◽  
Asexual Blood Stage ◽  
Adults And Children ◽  
A Prospective Study

Abstract Background Chloroquine is effective against the asexual blood stage of Plasmodium vivax. A high proportion of children are underdosed with the drug, but there are no studies comparing chloroquine exposure in adults and children aged 8–11 years old. The present study intends to compare these populations using the area under the curve (AUC) derived from the plasma concentration-time profile in patients with P. vivax. Methods A prospective study of cases was performed on male children (aged 9–11 years) and adults with vivax malaria. Blood samples were collected after several days of treatment. Chloroquine was measured by high-performance liquid chromatography. A non-compartmental pharmacokinetic model was used to calculate the pharmacokinetic parameters of the drug. Results A total of 20 children and 25 adults were included in the study. Plasma concentrations of chloroquine in older children ranged from 67 to 1112 ng/ml, and in adults the value ranged from 74 to 1147 ng/ml. The AUC to the last measurable concentration and to infinite was significantly lower in children than in adults, indicating a lower exposure to the drug. Conclusion These data demonstrate lower exposure to chloroquine in children, which corroborates the importance of optimising the doses of chloroquine in the study age band to ensure adequate exposure to the drug.

scholarly journals Pharmacokinetic Study of Modafinil in Relation to Gender and Ethnicity in Healthy Young Chinese Volunteers

2010 ◽  
Vol 13 (3) ◽  
pp. 443 ◽  
Author(s):  
Tao Guo ◽  
Longshan Zhao ◽  
Dong-Ya Xia
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
High Performance ◽  
Area Under The Curve ◽  
Total Body Weight ◽  
Apparent Volume ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Significant Difference ◽  
Total Body

Purpose. The pharmacokinetics of modafinil were investigated in relation to gender and ethnicity in healthy young volunteers from Han, Mongolian, Korean, Uygur and Hui ( n = 10/group) following administration of a single 200 mg oral dose. Methods. Blood samples were collected over 48 h for the determination of plasma levels of modafinil and its acid metabolite by High performance liquid chromatography with an ultraviolet detector. Pharmacokinetic parameters were evaluated using noncompartmental methods. Results. Modafinil was well tolerated and safe at a single oral dose of 200 mg. All participants reported adverse events, none of which was serious or unexpected. The maximum plasma concentration (Cmax) and area under the curve for modafinil concentration versus time, which was extrapolated to infinity (AUC0-∞), were higher in women compared to men (p < 0.01). No gender-based difference was noted in the total body weight-normalized modafinil oral clearance. The total body weight-normalized modafinil apparent volume of distribution and the t1/2 was found to exhibit an ethnicity-based significant difference. Conclusion. The results of the current study suggest that there might be pharmacokinetic differences related to gender and ethnicity in the pharmacokinetics of modafinil.

Lack of Pharmacokinetic Interaction Between the Antimigraine Compound, Almotriptan, and Propranolol in Healthy Volunteers

Cephalalgia ◽  
2001 ◽  
Vol 21 (1) ◽  
pp. 61-65 ◽  
Author(s):  
JC Fleishaker ◽  
TA Sisson ◽  
BJ Carel ◽  
NE Azie
Keyword(s):  
High Performance ◽  
Treatment Effects ◽  
Vital Signs ◽  
Area Under The Curve ◽  
Pharmacokinetic Interaction ◽  
Concomitant Administration ◽  
Crossover Design ◽  
Pharmacokinetic Parameters ◽  
Percent Confidence Interval ◽  
Healthy Male

This study was designed to assess the pharmacokinetics of almotriptan, a 5-HT1B/1D agonist, when administered in the presence and absence of propranolol. Healthy male ( n = 10) and female ( n = 2) volunteers received (i) 80 mg propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii) 12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by high performance liquid chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance (anova). Statistically significant differences between treatments in area under the curve (AUC), clearance, and half-life were observed ( P < 0.03), but these differences were < 7%. Ninety percent confidence interval analysis of log-transformed pharmacokinetic parameters showed that the treatments were equivalent. Adverse events were mild to moderate in intensity, and no treatment effects on vital signs were observed. The results show that propranolol has no effect on the pharmacokinetics of almotriptan. Concomitant administration of the two drugs is well tolerated.

Comparative Bioavailability of Praziquantel Tablets

DICP ◽  
1989 ◽  
Vol 23 (1) ◽  
pp. 29-32 ◽  
Author(s):  
Sming Kaojarern ◽  
Surapol Nathakarnkikool ◽  
Uthai Suvanakoot
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Disintegration Time ◽  
Maximum Serum ◽  
British Pharmacopoeia ◽  
Elimination Half ◽  
Comparative Bioavailability ◽  
Maximum Serum Concentration

Six different brands of 600 mg praziquantel tablets were evaluated. In vitro studies demonstrated that all but one of the products met the British Pharmacopoeia 1980 disintegration time specifications. The comparative bioavailability of four of the internationally available brands of praziquantel tablets were then studied in eight healthy volunteers using a crossover design. Serum praziquantel levels were determined by high-performance liquid chromatography. Individual serum profiles were analyzed for pharmacokinetic parameters such as maximum serum concentration, time to reach maximum, and area under the curve. Following administration of praziquantel 40 mg/kg po, the mean peak serum concentrations and the time to reach the peak ranged from 1.007 to 1.625 μg/ml and from 1.72 to 2.81 hours, respectively. The elimination half-life of praziquantel was 1.15 (0.94–1.25) hours. Differences greater than 20 percent (p < 0.05) were noted for these parameters between the original brand and the generic formulations. The relative bioavailabilities of the generic praziquantel formulations, with respect to the original brand, were 91.25, 80.95, and 69.86 percent. This is due to the failure of disintegration and subsequently poor dissolution. The effect of 30 percent reduction of bioavailability may lead to unacceptably high rates of treatment failure.

scholarly journals Pharmacokinetics of Ganciclovir during Continuous Venovenous Hemodiafiltration in Critically Ill Patients

2013 ◽  
Vol 58 (1) ◽  
pp. 94-101 ◽  
Author(s):  
Thomas Horvatits ◽  
Reinhard Kitzberger ◽  
Andreas Drolz ◽  
Christian Zauner ◽  
Walter Jäger ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
High Performance ◽  
Area Under The Curve ◽  
Antiviral Agent ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Target Area ◽  
Continuous Venovenous Hemodiafiltration

ABSTRACTGanciclovir is an antiviral agent that is frequently used in critically ill patients with cytomegalovirus (CMV) infections. Continuous venovenous hemodiafiltration (CVVHDF) is a common extracorporeal renal replacement therapy in intensive care unit patients. The aim of this study was to investigate the pharmacokinetics of ganciclovir in anuric patients undergoing CVVHDF. Population pharmacokinetic analysis was performed for nine critically ill patients with proven or suspected CMV infection who were undergoing CVVHDF. All patients received a single dose of ganciclovir at 5 mg/kg of body weight intravenously. Serum and ultradiafiltrate concentrations were assessed by high-performance liquid chromatography, and these data were used for pharmacokinetic analysis. Mean peak and trough prefilter ganciclovir concentrations were 11.8 ± 3.5 mg/liter and 2.4 ± 0.7 mg/liter, respectively. The pharmacokinetic parameters elimination half-life (24.2 ± 7.6 h), volume of distribution (81.2 ± 38.3 liters), sieving coefficient (0.76 ± 0.1), total clearance (2.7 ± 1.2 liters/h), and clearance of CVVHDF (1.5 ± 0.2 liters/h) were determined. Based on population pharmacokinetic simulations with respect to a target area under the curve (AUC) of 50 mg · h/liter and a trough level of 2 mg/liter, a ganciclovir dose of 2.5 mg/kg once daily seems to be adequate for anuric critically ill patients during CVVHDF.

Phase I clinical and pharmacokinetic study of oral etoposide phosphate.

1995 ◽  
Vol 13 (1) ◽  
pp. 200-209 ◽  
Author(s):  
C Sessa ◽  
M Zucchetti ◽  
T Cerny ◽  
O Pagani ◽  
F Cavalli ◽  
...  
Keyword(s):  
Phase I ◽  
Intravenous Administration ◽  
High Performance ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Oral Etoposide ◽  
Validation Data ◽  
Etoposide Phosphate

PURPOSE To determine the bioavailability (F) and the pharmacokinetic profile of both etoposide and its prodrug, etoposide phosphate, after oral and intravenous administration of etoposide phosphate, and to determine the maximum-tolerable dose (MTD) of oral etoposide phosphate administered daily for 5 consecutive days every 3 weeks. In addition, we sought to develop and validate two limited-sampling models (LSMs) to predict the etoposide area under the curve (AUC) 24 hours after administration of oral and intravenous etoposide phosphate. PATIENTS AND METHODS In the F part of the study, patients were assessed for pharmacokinetic studies after one oral and one intravenous administration of the same dose of etoposide phosphate. Etoposide phosphate and etoposide plasma concentrations were assayed by high-performance liquid chromatography (HPLC). To develop LSMs after oral and intravenous administration, patients were randomized between the training and validation data sets. In the phase I part of the study, which followed the F part, the dose of etoposide phosphate was escalated from 50 mg/m2/d for etoposide equivalents for 5 days to 220 mg/m2/d for 5 days. RESULTS Forty adult patients with solid tumors or lymphoma entered the study and 35 were assessable for toxicity. The MTDs were defined as 175 mg/m2 and 220 mg/m2 in previously treated and untreated patients, respectively. Neutropenia was dose-limiting, with high interpatient variability. Within 15 minutes after intravenous administration, etoposide phosphate was no longer detectable in plasma, and it was never detectable after oral administration. Plasma concentrations and pharmacokinetic parameters of etoposide following etoposide phosphate were comparable to those reported for etoposide. The relative F (mean +/- SD) of etoposide after oral etoposide phosphate was 76 +/- 27%, with a range of 37% to 144%. CONCLUSION The clinical and pharmacokinetic results of this study confirm the prodrug hypothesis of etoposide phosphate. Although firm conclusions cannot be drawn, the F of oral etoposide phosphate seems to be comparable to or only slightly better than that of oral etoposide.

Pharmacokinetics of undiluted or diluted high-dose etoposide with or without busulfan administered to patients with hematologic malignancies.

1994 ◽  
Vol 12 (7) ◽  
pp. 1468-1474 ◽  
Author(s):  
K Mross ◽  
P Bewermeier ◽  
W Krüger ◽  
M Stockschläder ◽  
A Zander ◽  
...  
Keyword(s):  
High Performance ◽  
Drug Exposure ◽  
Area Under The Curve ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Pharmacokinetic Data ◽  
Blood Samples ◽  
Systemic Drug Exposure ◽  
Systemic Drug

PURPOSE We used two different methods to administer high-dose etoposide (VP-16) during a myeloablative conditioning chemotherapy regimen before bone marrow transplantation (BMT). VP-16 was administered either diluted (0.5 mg/mL) or undiluted (20 mg/mL), with or without busulfan. PATIENTS AND METHODS Blood samples were drawn from 17 patients during the infusion (6 hours) and thereafter daily until 2 days after BMT. VP-16 concentrations were measured in all plasma samples by high-performance liquid chromatography (HPLC) and electrochemical detection, and the results were analyzed with a pharmacokinetic data analysis system. RESULTS All calculated pharmacokinetic parameters in the two patient groups (VP-16 administered diluted or undiluted) were similar. There were no statistically significant differences in half-lives, mean residence time (MRT), volume of distribution, total clearance, or area under the curve (AUC). VP-16 was found in blood samples from eight of 17 patients at the time of BMT. Significant differences in systemic drug exposure and systemic clearance were found when patients were grouped according to treatment with busulfan or with total-body irradiation (TBI). CONCLUSION The two administration modes for VP-16, either diluted or undiluted, are bioequivalent in pharmacokinetic terms. The terminal half-lives were longer than expected and resulted in significant VP-16 plasma levels at the time of BMT. The biologic significance remains unclear. Busulfan and/or concomitant medication with phenytoin influence plasma clearance (clp) and systemic drug exposure significantly.

scholarly journals Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1057
Author(s):  
Błażej Poźniak ◽  
Marta Tikhomirov ◽  
Kamila Bobrek ◽  
Paweł Jajor ◽  
Marcin Świtała
Keyword(s):  
High Performance ◽  
Allometric Scaling ◽  
Interindividual Variability ◽  
Dosage Adjustment ◽  
Age Groups ◽  
Area Under The Curve ◽  
Internal Exposure ◽  
Age Dependent ◽  
Non Linear ◽  
Selection For

Turkeys’ body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for resistance. The study aimed to investigate whether a non-linear dosage based on a published allometric model for tylosin clearance, may optimize the internal exposure in growing turkeys. The single dose PK study was performed on turkeys aged 6, 9.5, 13 and 17 weeks (BW from 1.75 kg to 15.75 kg). Tylosin was administered intravenously (i.v.) or orally (p.o.) according to following protocols: Dose = 31.6 × BW0.58 or Dose = 158 × BW0.58, respectively. Plasma tylosin was measured using high-performance liquid chromatography and non-compartmental PK analysis was performed. The area under the curve (AUClast) after i.v. administration was 8.90 ± 1.01; 7.51 ± 1.11; 6.54 ± 1.20 and 8.01 ± 1.75 mg × h/L in 6-; 9.5-; 13- and 17-week-old turkeys, respectively. After p.o. administration AUClast was 4.80 ± 2.92; 4.60 ± 2.45; 3.00 ± 1.49 and 3.24 ± 2.00 mg × h/L in respective age groups indicating high variability. For i.v. administration, the non-linear dosage allowed to minimize the age-dependent variability in AUC. However, due to low oral bioavailability (8–12%) and resulting interindividual variability, the proposed approach may not improve tylosin efficacy in turkeys under farm conditions.

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