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.

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.

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.

scholarly journals Are Prophylactic and Therapeutic Target Concentrations Different?: the Case of Lopinavir-Ritonavir or Lamivudine Administered to Infants for Prevention of Mother-to-Child HIV-1 Transmission during Breastfeeding

2016 ◽  
Vol 61 (2) ◽  
Author(s):  
Frantz Foissac ◽  
Jörn Blume ◽  
Jean-Marc Tréluyer ◽  
Thorkild Tylleskär ◽  
Chipepo Kankasa ◽  
...  
Keyword(s):  
South African ◽  
Population Analysis ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Pharmacokinetic Parameters ◽  
Breastfed Infants ◽  
Trough Concentrations ◽  
Therapeutic Doses ◽  
Mother To Child ◽  
Hiv 1

ABSTRACT The ANRS 12174 trial assessed the efficacy and tolerance of lopinavir (LPV)-ritonavir (LPV/r) prophylaxis versus those of lamivudine (3TC) prophylaxis administered to breastfed infants whose HIV-infected mothers were not on antiretroviral therapy. In this substudy, we assessed LPV/r and 3TC pharmacokinetics to evaluate the percentage of infants with therapeutic plasma concentrations and to discuss these data in the context of a prophylactic treatment. Infants from the South African trial site underwent blood sampling for pharmacokinetic study at weeks 6, 26, and 38 of life. We applied a Bayesian approach to derive the 3TC and LPV pharmacokinetic parameters on the basis of previously published pharmacokinetic models for HIV-infected children. We analyzed 114 LPV and 180 3TC plasma concentrations from 69 infants and 92 infants, respectively. A total of 30 LPV and 20 3TC observations were considered missing doses and discarded from the Bayesian analysis. The overall population analysis showed that 30 to 40% of the infants did not reach therapeutic targets, regardless of treatment group. The median LPV trough concentrations at weeks 6, 26, and 38 were 2.8 mg/liter (interquartile range [IQR], 1.7 to 4.4 mg/liter), 5.6 mg/liter (IQR, 3.2 to 7.7 mg/liter), and 3.4 mg/liter (IQR, 2.3 to 7.3 mg/liter), respectively. The median 3TC area under the curve from 0 to 12 h after the last drug intake were 5.6 mg · h/liter (IQR, 4.1 to 7.8 mg · h/liter), 5.9 mg · h/liter (IQR, 5.1 to 7.5 mg · h/liter), and 7.3 mg · h/liter (IQR, 4.9 to 8.5 mg · h/liter) at weeks 6, 26, and 38, respectively. Use of the therapeutic doses recommended by the WHO would have resulted in a higher proportion of infants achieving the targets. However, no HIV-1 infection was reported among these infants. These results suggest that the prophylactic targets for both 3TC and LPV may be lower than the therapeutic ones. For treatment, the WHO dosing guidelines should be suitable to maintain values above the therapeutic pharmacokinetic targets in most infants. (This study has been registered at ClinicalTrials.gov under identifier NCT00640263.)

scholarly journals Comparative Study on Pharmacokinetics of Four Long-Acting Injectable Formulations of Enrofloxacin in Pigs

2021 ◽  
Vol 7 ◽  
Author(s):  
Salah Uddin Ahmad ◽  
Jichao Sun ◽  
Fusheng Cheng ◽  
Bing Li ◽  
Safia Arbab ◽  
...  
Keyword(s):  
Comparative Study ◽  
High Performance ◽  
Pasteurella Multocida ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Maximum Plasma ◽  
Reference Formulation ◽  
Time Curve ◽  
Drug Concentrations ◽  
Long Acting

A comparative study on pharmacokinetics of four long-acting enrofloxacin injectable formulations was investigated in 36 healthy pigs after intramuscular injection according to the recommended single dose @ 2.5 mg/kg body weight. The drug concentrations in the plasma were computed using high-performance liquid chromatography (HPLC) with fluorescence detection. WinNonLin5.2.1 software was used to analyze the experimental data and compared it under one-way ANOVA using SPSS software with a 95% confidence interval (CI). The main pharmacokinetic parameters, that is, the maximum plasma concentrations (Cmax), the time to maximum concentration (Tmax), area under the time curve concentration (AUCall) and Terminal half-life (T1/2) were 733.84 ± 129.87, 917.00 ± 240.13, 694.84 ± 163.49, 621.98 ± 227.25 ng/ml, 2.19 ± 0.0.66, 1.50 ± 0.37, 2.89 ± 0.24, 0.34 ± 0.13 h, 7754.43 ± 2887.16, 8084.11 ± 1543.98, 7369.42 ± 2334.99, 4194.10 ± 1186.62 ng h/ml, 10.48 ± 2.72, 10.37 ± 2.38, 10.20 ± 2.81, and 10.61 ± 0.86 h for 10% enrofloxacin (Alkali), 20% enrofloxacin (Acidic), Yangkang and control drug Nuokang® respectively. There were significant differences among Cmax, Tmax, and AUCall of three formulations compare with that of the reference formulation. No significant differences were observed among the T1/2 for tested formulations compare with the reference formulation. The pharmacokinetic parameters showed that the tested formulations were somewhat better compared to the reference one. The calculated PK/PD indices were effective for bacteria such as Actinobacillus pleuropneumoniae and Pasteurella multocida with values higher than the cut-off points (Cmax/MIC90≥10–12 and AUC/MIC90 ≥ 125). However, they were not effective against bacteria like Haemophilus parasuis, Streptococcus suis, E. coli, and Bordetella bronchiseptica where lower values were obtained.

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.

Pharmacokinetics and metabolism of 4'-iodo-4'-deoxy-doxorubicin in humans.

1992 ◽  
Vol 10 (7) ◽  
pp. 1183-1190 ◽  
Author(s):  
J Robert ◽  
J P Armand ◽  
S Huet ◽  
M Klink-Alakl ◽  
G Recondo ◽  
...  
Keyword(s):  
Blood Cell ◽  
High Performance ◽  
Parent Compound ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Parent Drug ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Hematologic Toxicity ◽  
Cell Counts

PURPOSE 4'-iodo-4'-deoxydoxorubicin is a new anthracycline that currently is under clinical evaluation. To improve the management of future trials, we have determined its pharmacokinetics and metabolism during a phase I/II study and have tried to relate the parameters obtained to the hematologic toxicity of the drug in terms of the survival of blood cells. PATIENTS AND METHODS The pharmacologic study included 19 patients who were entered at dose levels that ranged between 6 and 90 mg/m2; nine patients were treated at 80 mg/m2, which is close to the maximum recommended dose level. Blood sampling was performed from the end of the bolus infusion to 48 hours after treatment. Drug and metabolites were extracted and analyzed by high-performance liquid chromatography (HPLC), and the data were processed by nonlinear fitting to multicompartment models. RESULTS Plasma concentrations were best fitted to a three-compartment model with half-lives of 5.2 minutes, 0.79 hours, and 10.3 hours. The total body clearance and volume of distribution at steady state were high (350 L/h/m2 and 2,065 L/m2). The drug was metabolized extensively to a 13-dihydroderivative, 4'-iodo-4'-deoxy-doxorubicinol; the mean area under the curve (AUC) ratio metabolite/parent drug was the highest observed ever for an anthracycline (12.1 +/- 7.4); the metabolite was cleared from the plasma with an elimination half-life of 15.3 hours. The AUCs of the parent compound and its metabolite were related linearly to the dose administered, and showed no saturation phenomenon. Urinary excretion was studied in nine patients and showed a cumulative elimination of less than 6% of the dose administered, two thirds of which were eliminated in the first 12 hours after injection. Ninety-three percent to 100% of the elimination of fluorescent compounds occurred in the form of the metabolite. Drug concentration in five tumor samples showed a rapid uptake of the drug from plasma and a preferential uptake of the parent drug compared with the metabolite. Blood cell counts after 4'-iodo-4'-deoxydoxorubicin treatment showed significant correlations among the surviving fractions of both granulocytes and platelets and the AUCs of the parent drug and its metabolite; the most significant correlations were obtained for the granulocytes and the metabolite. Significant correlations between AUCs and blood-cell survivals were maintained, even if only the nine patients treated at the dose of 80 mg/m2 were taken into account for the computation. CONCLUSIONS Our results especially show that myelosuppression that is induced by 4'-iodo-4'-deoxydoxorubicin can be well predicted by the measure of the AUC of the drug and its metabolite. This could be used for the further development of the drug toward high-dosage schedules.

Pharmacokinetic comparison of two buprenorphine formulations after buccal administration in healthy male cats

2017 ◽  
Vol 20 (4) ◽  
pp. 312-318 ◽  
Author(s):  
Brett M Gulledge ◽  
Kristen M Messenger ◽  
Karen K Cornell ◽  
Heather Lindell ◽  
Chad W Schmiedt
Keyword(s):  
Liquid Chromatography ◽  
Maximum Concentration ◽  
High Performance ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Storage Condition ◽  
Healthy Male ◽  
Limit Of Quantification ◽  
Significant Difference ◽  
Extent Of Absorption

Objectives The objective of this study was to compare the pharmacokinetics of compounded and commercially available aqueous formulations of buprenorphine after a single buccal dose to healthy cats and to evaluate the concentrations of a compounded buprenorphine solution over 21 days when stored at room temperature (RT; 22–24°C) with exposure to light or when refrigerated at 4°C while protected from light. Methods Six young healthy male cats were administered single buccal doses of compounded and commercially available formulations of buprenorphine (0.03 mg/kg) using a randomized, blinded, two-period crossover design. Blood samples were obtained over a 24 h period and plasma buprenorphine concentrations were determined using ultra-high-pressure liquid chromatography with mass spectrometry detection. Three batches of the compounded formulation were stored at RT or 4°C and aliquots were evaluated over 21 days for buprenorphine concentration using high-performance liquid chromatography with fluorescence detection. Results Plasma concentrations of buprenorphine were above the limit of quantification up to 6 h in some cats and up to 3 h in all cats. The area under the curve was significantly less for the compounded formulation ( P = 0.004). A significant difference was not detected between formulations for time to maximum concentration ( P = 0.11), maximum concentration ( P = 0.06), half-life ( P = 0.88) and mean residence time ( P = 0.57). Buprenorphine concentration in the compounded formulation was not affected by storage condition or time and remained between 90% and 110% of the target concentration at all time points. Conclusions and relevance A buprenorphine solution prepared from sublingual tablets is absorbed after buccal administration in healthy cats. The extent of absorption is significantly less than that of the commercially available formulation. The compounded solution maintains an acceptable buprenorphine concentration for at least 21 days when stored at RT or refrigerated.

Pharmacokinetics and investigation of optimal dose ertapenem in intermittent hemodialysis patients

2018 ◽  
Vol 34 (10) ◽  
pp. 1766-1772 ◽  
Author(s):  
Lama M Hsaiky ◽  
Francine D Salinitri ◽  
Judy Wong ◽  
Sin-Ling T Jennings ◽  
Neha H Desai ◽  
...  
Keyword(s):  
Half Life ◽  
Plasma Concentrations ◽  
Area Under The Curve ◽  
Optimal Dose ◽  
Hemodialysis Patients ◽  
Pharmacokinetic Parameters ◽  
Intermittent Hemodialysis ◽  
Pharmacokinetic Studies ◽  
Open Label ◽  
Serious Adverse Events

Abstract Background Previous pharmacokinetic studies demonstrated an increase in serum ertapenem concentrations with decreasing kidney function, including patients receiving renal replacement therapy. This study evaluated the pharmacokinetic parameters of ertapenem in patients receiving hemodialysis. Methods This prospective, single-center, open-label study examined the pharmacokinetics of a single intravenous (IV) dose of ertapenem 1 g in seven hospitalized noninfected patients undergoing hemodialysis. Blood samples were collected prior to ertapenem administration and at 0.5, 1, 2, 6, 12 and 48 hours (h) after administration. Ertapenem concentrations were determined by validated liquid chromatography mass spectrometry assay. Results Following an IV bolus of 1 g ertapenem, plasma concentrations declined relatively slowly with a mean ±standard deviation (SD) elimination half-life of 19.3 ±6.6 h. Plasma concentrations were similar in all subjects, with maximum mean plasma concentration observed of 343±48 µg/mL postdose. The mean ±SD values for systemic plasma clearance (CL) and volume of distribution at steady state (Vss) were 2±0.5 mL/min and 3295±1187 mL, respectively. The area under the curve for 0 h–∞ (AUCinf) was 7494 ±1424 h•µg/mL. No gender effect was observed and no serious adverse events were reported. Conclusions Ertapenem half-life was prolonged in hemodialysis patients. Considering the nonrenal clearance and the expected 70% removal with high-efficacy hemodialysis, the dose of 1 g ertapenem, three times weekly, after hemodialysis may produce pharmacodynamically sufficient exposure for potential antimicrobial efficacy. Further studies are warranted to assess the clinical efficacy and safety of this dose with prolonged duration of therapy.

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.

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