Anthelmintic Efficacy and Pharmacokinetics of Ivermectin Paste after Oral Administration in Mules Infected by Cyathostomins

Ivermectin (IVM) is an anthelmintic compound commonly used off-label in mules due to its broad-spectrum of activity. Despite the general use of IVM in mules with the same dose and route of administration licensed for horses, significant pharmacokinetic differences might exist between horses and mules, as already observed for donkeys. The aim of the present study was to evaluate the pharmacokinetic profile and anthelmintic efficacy of an oral paste of IVM in mules naturally infected with cyathostomins. Fifteen adult mules with fecal egg counts (FEC) ≥ 200 eggs per gram (EPG), with exclusive presence of cyathostomins, were included in the study. All mules were orally treated with IVM according to the manufacturer's recommended horse dosage (200 µg/kg body weight). FECs were performed before (day-10 and day-3) and after treatment at days 14 and 28 by using a modified McMaster method. The FEC reduction (FECR%) was also calculated. Blood samples were collected from five animals at various times between 0.5 h up to 30 days post treatment to determine pharmacokinetic parameters. The maximum IVM serum concentration (Cmax) was 42.31 ± 10.20 ng/mL and was achieved at 16.80 ± 9.96 h post-treatment (Tmax), area under the curve (AUC) was 135.56 ± 43.71 ng × day/mL. FECR% remained high (>95%) until the 28th day.

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PHARMACOKINETICS OF A SINGLE INTRAVENOUS INJECTION OF CEFQUINOME IN RABBITS

Mansoura Veterinary Medical Journal ◽

10.35943/mvmj.2018.19.1010 ◽

2018 ◽

pp. 307-319

Author(s):

Mohamed El-Sayed ◽

Magdy Amer ◽

Sameh El-nabtity ◽

Sara El-Azab

Keyword(s):

Body Weight ◽

High Performance Liquid Chromatography ◽

High Performance ◽

Plasma Concentrations ◽

Pharmacokinetic Profile ◽

Pharmacokinetic Parameters ◽

Post Injection ◽

Blood Samples ◽

Single Intravenous Injection ◽

New Zealand White Rabbits

The current study was carried out to investigate the pharmacokinetic profile of cefquinome following a single IV injection in ten New Zealand white rabbits (2-2.5 kg body weight). Cefquinome was injected intravenously (2mg/kg body weight) and blood samples were collected before drug administration and up to 24h after injection. Cefquinome plasma concentrations were measured using HPLC (high- performance liquid chromatography). The result showed that the plasma concentration of cefquinome was 9.13 ± 0.43 µg/mL at 5min post-injection then declined gradually to 0.73 ± 0.18µg/mL after 2 hours. No cefquinome concentration could be detected at 4h post injection. The major pharmacokinetic parameters (Mean ± SEM) were T1/2 λz 0.52 ± 0.05h, AUC0-∞ 9.13 ± 0.63 h*µg/mL, Cl 239.25 ±14.61 mL/h/kg, Vz 170.89 ± 9.7 mL/kg and MRT0-∞ 0.75 ±0.06 h.

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Pharmacokinetics of Ceftaroline in Normal Body Weight and Obese (Classes I, II, and III) Healthy Adult Subjects

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00498-15 ◽

2015 ◽

Vol 59 (7) ◽

pp. 3956-3965 ◽

Cited By ~ 14

Author(s):

Julie Ann Justo ◽

Stockton M. Mayer ◽

Manjunath P. Pai ◽

Melinda M. Soriano ◽

Larry H. Danziger ◽

...

Keyword(s):

Body Weight ◽

Healthy Adult ◽

Plasma Concentrations ◽

Area Under The Curve ◽

Total Body Weight ◽

Pharmacokinetic Profile ◽

Volume Of Distribution ◽

Population Pharmacokinetic ◽

Ceftaroline Fosamil ◽

Plasma And Urine Samples

ABSTRACTThe pharmacokinetic profile of ceftaroline has not been well characterized in obese adults. The purpose of this study was to evaluate the pharmacokinetics of ceftaroline in 32 healthy adult volunteers aged 18 to 50 years in the normal, overweight, and obese body size ranges. Subjects were evenly assigned to 1 of 4 groups based on their body mass index (BMI) and total body weight (TBW) (ranges, 22.1 to 63.5 kg/m2and 50.1 to 179.5 kg, respectively). Subjects in the lower-TBW groups were matched by age, sex, race/ethnicity, and serum creatinine to the upper-BMI groups. Serial plasma and urine samples were collected over 12 h after the start of the infusion, and the concentrations of ceftaroline fosamil (prodrug), ceftaroline, and ceftaroline M-1 (inactive metabolite) were assayed. Noncompartmental and population pharmacokinetic analyses were used to evaluate the data. The mean plasma ceftaroline maximum concentration and area under the curve were ca. 30% lower in subjects with a BMI of ≥40 kg/m2compared to those <30 kg/m2. A five-compartment pharmacokinetic model with zero-order infusion and first-order elimination optimally described the plasma concentration-time profiles of the prodrug and ceftaroline. Estimated creatinine clearance (eCLCR) and TBW best explained ceftaroline clearance and volume of distribution, respectively. Although lower ceftaroline plasma concentrations were observed in obese subjects, Monte Carlo simulations suggest the probability of target attainment is ≥90% when the MIC is ≤1 μg/ml irrespective of TBW or eCLCR. No dosage adjustment for ceftaroline appears to be necessary based on TBW alone in adults with comparable eCLCR. Confirmation of these findings in infected obese patients is necessary to validate these findings in healthy volunteers. (This study has been registered at ClinicalTrials.gov under registration no. NCT01648127.)

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Population Pharmacokinetics of Siplizumab (MEDI-507), a Humanized Anti-CD2 Monoclonal Antibody, in Cancer Patients.

Blood ◽

10.1182/blood.v114.22.2670.2670 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2670-2670

Author(s):

Chunlin Chen ◽

John E Janik ◽

Karen Kaucic ◽

Lorin Roskos ◽

Bahija Jallal ◽

...

Keyword(s):

Monoclonal Antibody ◽

Body Weight ◽

Serum Concentration ◽

Dose Escalation ◽

Pharmacokinetic Parameters ◽

Population Pharmacokinetic ◽

Serum Concentrations ◽

Concentration Data ◽

Non Linear ◽

Volumes Of Distribution

Abstract Abstract 2670 Poster Board II-646 Introduction: Siplizumab, a humanized IgG1k class monoclonal antibody that targets CD2 expressing T-and NK-cells, was evaluated in phase I dose-escalation trials in patients with CD2-positive lymphoproliferative disorder. The objective of this study was to develop a population pharmacokinetic (PK) model for siplizumab and identify covariates that could explain the variability in siplizumab pharmacokinetic parameters. Methods: A Phase 1, open label, dose-escalation study was conducted in 29 patients (14 males/15 females, age range 34–79 years) who received 0.2–4.8 mg/kg of siplizumab as 1-3 consecutive daily doses every 14 days for a total of 1-8 cycles. Siplizumab serum concentration data was analyzed using a nonlinear mixed effects modeling approach with software (NONMEM). Based on exploratory analysis, 1-and 2-compartment non-linear models were evaluated. Demographic covariates including body weight, age, sex and race (Caucasian/Black/Asian) were screened using Generalized Additive Model (GAM) analysis. Covariates selected during the GAM analysis were further tested for significance in NONMEM using the forward inclusion and backward elimination approach. Results: Siplizumab concentrations were obtained from all 29 patients in the study yielding a total of 619 serum concentration observations. Pronounced non-linearity in siplizumab serum concentrations was observed after the initial and later dosing cycles, with serum concentrations declining faster at lower dose levels. The data was best described by a two-compartment pharmacokinetic model with zero-order input with parallel linear and non-linear elimination pathways. Goodness of fit plots and model diagnostics indicated good agreement between observed and model predicted serum concentration values. The population estimates for linear clearance was 0.168 L/day with inter-subject variability (ISV) of 50%, and inter-compartmental clearance was 2.83 L/day. Nonlinear elimination parameters, Vmax and Km were 10.32 mcg/day (56% ISV) and 51.8 mcg/L, respectively. Sex of the patients was identified as a significant covariate impacting volumes of distribution. Male patients had higher central and peripheral volumes of distribution of 2.8 L and 3.0 L, respectively, compared to1.38 L and 2.4 L in females [32% vs 50% ISV]. Conclusion: The serum concentration-time profile of siplizumab was adequately described by a two-compartment non-linear PK model. Population parameters were precisely estimated and correspond well to reported PK behaviour of monocolonal antibodies with significant target mediated elimination. The lower volume distribution in females is most likely due to lower body weight compared to males in this study. The population PK model combined with pharmacodynamic data could serve as a tool to guide selection of optimal dose regimens for siplizumab. Disclosures: No relevant conflicts of interest to declare.

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

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/j3fk5r ◽

2010 ◽

Vol 13 (3) ◽

pp. 443 ◽

Cited By ~ 3

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.

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The effects of oral administration of Cola nitida on the pharmacokinetic profile of metoclopramide in rabbits

BMC Pharmacology and Toxicology ◽

10.1186/s40360-019-0379-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Cecilia Nwadiuto Amadi ◽

Wisdom Izuchukwu Nwachukwu

Keyword(s):

Drug Interaction ◽

Plasma Concentration ◽

Oral Administration ◽

Peak Plasma ◽

Peak Plasma Concentration ◽

Elimination Rate ◽

Area Under The Curve ◽

Pharmacokinetic Profile ◽

Pharmacokinetic Parameters ◽

Cola Nitida

Abstract Background Cola nitida is commonly chewed in many West African cultures to ease hunger pangs and sometimes for their stimulant and euphoriant qualities. Metoclopramide is a known substrate for P-gp, SULT2A1 and CYP2D6 and studies have revealed that caffeine- a major component of Cola nitida can induce P-glycoprotein (P-gp), SULT2A1 and SULT1A1, hence a possible drug interaction may occur on co-administration. The aim of this study was to investigate the pharmacokinetic interactions of Cola nitida and metoclopramide in rabbits. Methods The study was performed in two stages using five healthy male rabbits with a 1-week washout period between treatments. Stage one involved oral administration of metoclopramide (0.5 mg/kg) alone while in the second stage, metoclopramide (0.5 mg/kg) was administered concurrently with Cola nitida (0.7 mg/kg). Blood samples were collected after each stage at predetermined intervals and analyzed for plasma metoclopramide concentration using HPLC. Results Compared with control, the metoclopramide/Cola nitida co-administration produced a decrease in plasma concentration of metoclopramide at all the time intervals except at the 7th hour. The following pharmacokinetic parameters were also decreased: area under the curve (51%), peak plasma concentration (39%), half-life (51%); while an increase in elimination rate constant (113%) and clearance rate (98%) were noted indicating rapid elimination of the drug. A minimal decrease in absorption rate (10%) was also observed. Conclusions The results of this study reveal a possible herb-drug interaction between Cola nitida and metoclopramide.

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Effect of diabetes-specific nutrition formulas on satiety and hunger hormones in patients with type 2 diabetes

Nutrition and Diabetes ◽

10.1038/s41387-019-0093-x ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Adham Mottalib ◽

Martin J. Abrahamson ◽

David M. Pober ◽

Rani Polak ◽

Ahmed H. Eldib ◽

...

Keyword(s):

Type 2 Diabetes ◽

Weight Loss ◽

Body Weight ◽

Peptide Yy ◽

Area Under The Curve ◽

Body Weight Loss ◽

Nutrition Therapy ◽

Blood Samples ◽

Reduce Body Weight

Abstract Objectives Diabetes-specific nutritional formulas (DSNFs) are frequently used by patients with type 2 diabetes (T2D) as part of nutrition therapy to improve glycemic control and reduce body weight. However, their effects on hunger and satiety hormones when compared to an isocaloric standardized breakfast are not fully understood. This study aims to evaluate the postprandial effects of two DSNFs—Glucerna (GL) and Ultra Glucose Control (UGC)—versus oatmeal on selected satiety and hunger hormones. Method After an overnight fast, 22 patients with T2D (mean age 62.3 ± 6.8 years, A1C 6.8 ± 0.7%, body weight 97.4 ± 21.3 kg, and BMI 33.2 ± 5.9 kg/m²) were given 200 kcal of each meal on three separate days. Blood samples for amylin, cholecystokinin (CCK), ghrelin, glucagon, leptin, and peptide-YY (PYY) were collected at baseline and 30, 60, 90, 120, 180, and 240 min after the start of each meal. Incremental area under the curve (iAUC0-240) for each hormone was calculated. Results iAUC0-240 for glucagon and PYY were significantly higher after GL and UGC than after oatmeal (p < 0.001 for both). No difference was observed between the three meals on postprandial amylin, CCK, ghrelin, and leptin hormones. Conclusions Intake of DSNFs significantly increases secretion of PYY and glucagon, two important satiety hormones. While subjective satiety was not directly evaluated, the increased effect on satiety hormones may partially explain the mechanism of body weight loss associated with DSNF use.

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Population Pharmacokinetics of Enoxaparin in Children at Risk for Symptomatic Thromboembolism.

Blood ◽

10.1182/blood.v114.22.1071.1071 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1071-1071

Author(s):

Mirjam Nadine Trame ◽

Lesley Mitchell ◽

Christoph Male ◽

Jeffrey S. Barrett ◽

Georg Hempel ◽

...

Keyword(s):

Body Weight ◽

Population Pharmacokinetics ◽

Maintenance Dose ◽

Factor Xa ◽

Volume Of Distribution ◽

Pharmacokinetic Parameters ◽

Population Pharmacokinetic ◽

Safety And Efficacy ◽

Off Label ◽

Final Population

Abstract Abstract 1071 Poster Board I-93 Introduction: Enoxaparin, a low-molecular-weight-heparin (LMWH), is used off-label in children to prevent symptomatic thromboembolism when acute anticoagulation or secondary prevention is required due to venous thrombosis or stroke. This investigation was conducted because of concerns of altered pharmacokinetics and a lack of safety and efficacy data when used in children. Patients and Methods: Data of 126 children and adolescents with a median age of 5.9 years receiving enoxaparin either as a once or twice daily dosing regimen were analyzed. Children < 12 months of age received a starting dose of 1.5 mg/kg followed by a maintenance dose of 1.3 mg/kg. Children > 12 months of age were started on 1 mg/kg followed by a maintenance dose of 1 mg/kg. Blood samples were drawn after patients reached steady-state on their maintenance dose at baseline prior to the next dose, and at 2, 4, 8 and 12 hours after administration. The median enoxaparin concentration in our population resulted in a median anti-factor Xa activity of 0.4 U/ml (range 0 – 1 U/ml anti-factor Xa). By means of population pharmacokinetics using nonlinear mixed-effects modelling (NONMEM) plasma concentration-time data were analyzed. Several covariates such as age, body weight and body surface area were tested on their effects on the pharmacokinetic parameters. Results: Using a two-compartment model the enoxaparin kinetics were described sufficiently. By using body weight and age as covariates for clearance (CL) and central volume of distribution (V1) the best results were obtained. The final population estimates of enoxaparin resulted to be: CL 7.11 ml h-1 kg-1 ± 14.3%, V1 7.31 ml kg-1 ± 33.5%, intercompartimental clearance (Q) 194 ml h-1 ± 24.7%, peripheral volume of distribution (V2) 45.1 l ± 52.5% and absorption rate (ka) 0.0799 h-1 ± 21.7% (estimates ± standard errors). Interindividual variability (IIV) was found to be 75.6% for CL and 78.4% for Q, respectively. Figure 1 shows the predicted activity time-course versus the measured activities for a representative patient. The model is capable of describing all aging and dosing groups of our childhood population (neonates, infants to adolescents). Conclusion: The high IIV in CL and Q in our population underlines the need for monitoring the activity and individualizing the dose. Further population pharmacokinetic/-dynamic investigations should be conducted to predict target enoxaparin levels or other new antithrombotic drugs for more safety and efficacy during antithrombotic therapy when used in children. Disclosures: Off Label Use: Enoxaparin (LMWH) is used off-label in children to prevent symptomatic thromboembolism..

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Is the Recommended Once-Daily Dose of Lamivudine Optimal in West African HIV-Infected Children?

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00306-10 ◽

2010 ◽

Vol 54 (8) ◽

pp. 3280-3286 ◽

Cited By ~ 7

Author(s):

Naïm Bouazza ◽

Déborah Hirt ◽

Christophe Bardin ◽

Serge Diagbouga ◽

Boubacar Nacro ◽

...

Keyword(s):

Body Weight ◽

Area Under The Curve ◽

Compartment Model ◽

Individual Characteristics ◽

Pharmacokinetic Parameters ◽

Population Pharmacokinetic ◽

Parameter Estimates ◽

Ratio Test ◽

Once Daily ◽

Time Courses

ABSTRACT We aimed in this study to describe lamivudine concentration-time courses in treatment-naïve children after once-daily administration, to study the effects of body weight and age on lamivudine pharmacokinetics, and to simulate an optimized administration scheme. For this purpose, lamivudine concentrations were measured in 49 children after at least 2 weeks of didanosine-lamivudine-efavirenz treatment. A total of 148 plasma lamivudine concentrations were measured, and a population pharmacokinetic model was developed with NONMEM. The influence of individual characteristics was tested using a likelihood ratio test. Children were divided into two groups, according to their pharmacokinetic parameters, thanks to tree regression analysis. For each patient, the area under the curve was derived from estimated individual pharmacokinetic parameters. Different once-daily doses were simulated in each group, to obtain the same exposure in children as the mean effective exposure in adults (8.9 mg/liter·h). A two-compartment model in which the slope of distribution is assumed to be equal to the absorption rate constant adequately described the data. Parameter estimates were standardized for a mean standard body weight using an allometric model. Children were then divided into 2 groups according to body weight: CL/F was significantly higher in children weighing less than 17 kg (1.12 liters/h/kg) than in children over 17 kg (0.95 liters/h/kg; P = 0.01). The target mean AUC of 8.9 mg/liters·h was obtained with a 10-mg/kg once-daily lamivudine (3TC) dose for children below 17 kg; the recommended dose of 8 mg/kg seems to be sufficient in children weighing more than 17 kg. These assumptions should be prospectively confirmed.

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

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.7.1468 ◽

1994 ◽

Vol 12 (7) ◽

pp. 1468-1474 ◽

Cited By ~ 26

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.

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Pharmacokinetic Profile of Curcumin and Nanocurcumin in Plasma, Ovary, and Other Tissues

Drug Research ◽

10.1055/a-0863-4355 ◽

2019 ◽

Vol 69 (10) ◽

pp. 559-564 ◽

Cited By ~ 3

Author(s):

Wawaimuli Arozal ◽

Wenny Trias Ramadanty ◽

Melva Louisa ◽

Regina Puspa Utami Satyana ◽

Gaviota Hartono ◽

...

Keyword(s):

Ovarian Cancer ◽

Particle Size ◽

Pharmacokinetic Profile ◽

Pharmacokinetic Parameters ◽

Absorption Process ◽

Sprague Dawley ◽

Particle Size Reduction ◽

Blood Samples ◽

Sprague Dawley Rats ◽

Low Solubility

Abstract Background Curcumin is a natural diphenolic compound that is currently being investigated for various cancers, including ovarian cancer. Clinical application of curcumin has been limited due to its low solubility and bioavailability and rapid metabolism and degradation at physiological pH. Particle size is one factor that can affect the absorption process, which thus increases compound solubility and transport across the membrane. This study was conducted to determine the effects of modifying the particle size of curcumin on its pharmacokinetic parameters in blood and other organs. Methods Female Sprague Dawley rats were administered a single oral dose of 500 mg/kg curcumin or nanocurcumin. Blood samples were collected at 10, 15, 30, 45, 75, and 120 min, and ovaries, livers, kidneys, and colons were collected at 180 min. The levels of curcumin in plasma and organs were determined using UPLC-MS/MS, and the pharmacokinetic parameters were evaluated. Results Curcumin levels were detectable and measurable in plasma and organs of rats that were administered curcumin or nanocurcumin. Overall, no statistically significant differences were found in pharmacokinetic parameters between curcumin and nanocurcumin groups in both plasma and organs, except for ovaries. The curcumin levels in plasma, liver, kidney, and colon in the curcumin group were higher than those in the nanocurcumin group. However, curcumin concentrations in ovaries in the nanocurcumin group were 3.6 times higher than those in the curcumin group. Conclusion Particle size reduction of curcumin did not increase the concentration of curcumin in the plasma but increased its distribution in the ovaries.

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