Pharmacokinetic studies on Sulfamonomethoxine in rabbits

2019 ◽  
Vol 20 (2) ◽  
pp. 92-97
Author(s):  
M Amer ◽  
M Elsayed ◽  
S Kazawaki ◽  
W Fathy ◽  
Eman El-Ashry
Keyword(s):  
Half Life ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
The Body ◽  
Pharmacokinetic Studies ◽  
Plasma Drug ◽  
Time Data ◽  
Drug Concentrations ◽  
Two Compartment Model

The present study was performed to determine the pharmacokinetics of sulfamonomethoxine (20mg/kg) in 5 rabbits after its oral and intravenous administration. Blood samples were collected immediately before (time 0) and at 0.08, 0.25, 0.5, 1, 3, 5 and 8 hours post-dosing to evaluate the pharmacokinetics of sulfamonomethoxine. Plasma sulfamonomethoxine concentrations were quantified with HPLC-UV, and plasma drug concentration versus time data after IV was best fitted to the two-compartment model, characterized with the distribution phase (α) equaled to 2.05 h-1 with a distribution half-life [t0.5(α)] equaled to 0.61 h. The volume of distribution of (V1c) was 0.15 ml/kg., whereas the volume of distribution at a steady – state [Vdss] was 0.20 ml/kg, and the body clearance was 0.03 ml/ kg / h. After oral administration of SMM, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t1/2ab) and elimination (t1/2β) were 0.02 and 1.99 h, respectively. The maximal absorption concentration (Cmax) was estimated as 114.06 µg/ml at 0.12 h, and the Area under the curve (AUC) was 340.42 µg/ml/h.

scholarly journals 1119. Assessment of Vancomycin Pharmacokinetic Parameters in Pediatric Patients After Liver Transplantation

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S651-S652
Author(s):  
Ronaldo Morales ◽  
Vanessa D Juodinis ◽  
Daniela Carla de Souza ◽  
Silvia Regina C Jorge Santos
Keyword(s):  
Liver Transplantation ◽  
Therapeutic Target ◽  
Bacterial Infections ◽  
Pediatric Patients ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Critical Conditions ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies

Abstract Background Vancomycin is largely prescribed to treat gram-positive bacterial infections in pediatric patients after liver transplantation with the same empirical doses prescribed in other critical conditions due to the absence of pharmacokinetic studies in this population. The objective of this investigation was to describe the vancomycin pharmacokinetic parameters and to assess the vancomycin percentage of target attainment with empirical regimen. Methods Prospective and longitudinal study with pediatric post-liver transplantation patients who received at least 48 hours of vancomycin between January 2020 and May 2021. Patients with acute or chronic renal failure or receiving renal replacement therapy were excluded. Vancomycin therapy started with 40-60mg/kg daily, one-hour infusion. The pharmacokinetic parameters were determined by one-compartment model with first-order kinetics using near steady-state postdistributional peak and trough within the same dosing interval. Therapeutic target was defined as vancomycin 24-hour area under the curve/minimum inhibitory concentration (AUCss0-24/MIC) ≥ 400 and < 600. The study protocol was approved by the local ethics committee. Results We included 18 sets of peak/trough serum concentrations obtained from 12 patients. The patients had median age of 11 (interquartile range [IQ] 8-16) months. The found vancomycin clearance, volume of distribution and half-life values were, respectively, 2.1 (IQ 1.4-2.8) mL/kg/min, 0.6 (IQ 0.5-0.7) L/kg and 3.2 (IQ 2.3-4.0) hours. After the initial dose regimen, 5 (42%) patients reached the therapeutic target. Conclusion Using the one-compartment model, we evaluate the pharmacokinetic parameters of vancomycin in pediatric patients after liver transplantation. Most of patients did not reach the therapeutic target with empirical regimen, so it is prudent to monitor the exposure to vancomycin directly by AUC/MIC ratio to maximize antimicrobial efficacy. Disclosures All Authors: No reported disclosures

Steady-State Pharmacokinetics of Cefoperazone and Sulbactam in Patients with Acute Appendicitis

1994 ◽  
Vol 28 (6) ◽  
pp. 703-707
Author(s):  
Larry H. Danziger ◽  
Stephen C. Piscitelli ◽  
Donna J. Occhipinti ◽  
Daniel J. Resnick ◽  
Keith A. Rodvold
Keyword(s):  
Steady State ◽  
Acute Appendicitis ◽  
Dosage Reduction ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Hepatic Function ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Elimination Half ◽  
G Prior

OBJECTIVE: To determine the steady-state pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis. METHODS: Six patients with normal renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood samples were collected after each patient received at least three doses of cefoperazone/sulbactam. RESULTS: Cefoperazone and sulbactam could be best described by a two-compartment model. Mean ± SD values for cefoperazone steady-state volume of distribution (Vssd), elimination half-life (t1/2β), clearance (Cl), and area under the curve (AUC0-t) were 19.8 ± 8.0 L, 3.97 ± 1.06 h, 62.6 ± 16.3 mL/min, and 556.9 ± 122.0 mg·h/L, respectively. Sulbactam Vssd, t1/2β, Cl, and AUC0-t were 34.7 ± 13.9 L, 1.39 ± 0.4 h, 288.6 ± 68.2 mL/min, and 64.8 ± 24.5 mg·h/L, respectively. CONCLUSIONS: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increased Vssd and t1/2β in patients with acute appendicitis. An increased Vssd also was observed for sulbactam. The disposition of cefoperazone/sulbactam is altered in this group of patients; however, these changes are not likely to warrant a dosage reduction.

scholarly journals Pharmacokinetics of saquinavir, zidovudine, and zalcitabine in combination therapy.

1997 ◽  
Vol 41 (11) ◽  
pp. 2428-2432 ◽  
Author(s):  
G F Vanhove ◽  
H Kastrissios ◽  
J M Gries ◽  
D Verotta ◽  
K Park ◽  
...  
Keyword(s):  
Half Life ◽  
Area Under The Curve ◽  
Chronic Administration ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Pharmacokinetic Studies ◽  
Mean Values ◽  
Aids Clinical Trial Group ◽  
The Mean

We investigated the pharmacokinetics of zidovudine, zalcitabine, and saquinavir in AIDS Clinical Trial Group protocol 229. Patients received either saquinavir, zalcitabine, or a combination of both, together with zidovudine three times a day. Approximately 100 patients were enrolled in each treatment arm, and intensive pharmacokinetic studies were performed on about 25 patients per arm at weeks 1 and 12. We estimated the pharmacokinetic parameters of all three drugs by using parametric and nonparametric methods. The mean values of the pharmacokinetic parameters of zidovudine (clearance [CL]/bioavailability [F], 168 liters/h; volume of distribution [V]/F, 185 liters; half-life, 0.76 h) and zalcitabine (CL/F, 25 liters/h; V/F, 92.2 liters; half-life, 2.7 h) were similar to those reported previously. For saquinavir, the mean pharmacokinetic parameter estimates using parametric methods were as follows: maximum concentration of drug in serum [Cmax], 70.8 ng/ml; time to Cmax, 3.11 h; area under the curve, 809 ng x h/ml; CL/F, 989 liters/h; V/F, 1,503 liters; half-life, 1.38 h. For all three drugs, clearance decreased with age. Weight did not influence the clearance of zidovudine, but the clearance of zalcitabine and saquinavir increased with weight. There were no differences in pharmacokinetic parameters between study weeks and arms, suggesting that there is no change in kinetics with chronic administration and that there are no significant pharmacokinetic interactions among these three drugs.

scholarly journals Erythropoietin kinetics in rats: generation and clearance

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 646-649 ◽  
Author(s):  
SE Steinberg ◽  
JF Garcia ◽  
GR Matzke ◽  
J Mladenovic
Keyword(s):  
Intravenous Injection ◽  
Plasma Volume ◽  
Rat Model ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Disappearance Curve

Abstract Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

scholarly journals Pharmacokinetics and Efficacy of Piperaquine and Chloroquine in Melanesian Children with Uncomplicated Malaria

2007 ◽  
Vol 52 (1) ◽  
pp. 237-243 ◽  
Author(s):  
Harin A. Karunajeewa ◽  
Kenneth F. Ilett ◽  
Ivo Mueller ◽  
Peter Siba ◽  
Irwin Law ◽  
...  
Keyword(s):  
Half Life ◽  
Uncomplicated Malaria ◽  
Active Metabolite ◽  
High Performance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Elimination Half ◽  
Median Volume ◽  
Intensive Sampling

ABSTRACT The disposition of chloroquine (CQ) and the related 4-aminoquinoline, piperaquine (PQ), were compared in Papua New Guinean children with uncomplicated malaria. Twenty-two children were randomized to 3 days of PQ phosphate at 20 mg/kg/day (12 mg of PQ base/kg/day) coformulated with dihydroartemisinin (DHA-PQ), and twenty children were randomized to 3 days of CQ at 10 mg base/kg/day with a single dose of sulfadoxine-pyrimethamine (CQ-SP). After a 42-day intensive sampling protocol, PQ, CQ, and its active metabolite monodesethyl-chloroquine (DECQ) were assayed in plasma by using high-performance liquid chromatography. A two-compartment model with first-order absorption was fitted to the PQ and CQ data. There were no significant differences in age, gender, body weight, or admission parasitemia between the two groups. The PCR-corrected 42-day adequate clinical and parasitological responses were 100% for DHA-PQ and 94% for CQ-SP, but P. falciparum reinfections during follow-up were common (33 and 18%, respectively). For PQ, the median volume of distribution at steady state, allowing for bioavailability (V ss/F), was 431 liters/kg (interquartile range [IQR], 283 to 588 liters/kg), the median clearance (CL/F) was 0.85 liters/h/kg (IQR, 0.67 to 1.06 liters/h/kg), the median distribution half-life (t 1/2 α) was 0.12 h (IQR, 0.05 to 0.66 h), and the median elimination half-life (t 1/2 β) was 413 h (IQR, 318 to 516 h). For CQ, the median V ss/F was 154 liters/kg (IQR, 101 to 210 liters/kg), the median CL/F was 0.80 liters/h/kg (IQR, 0.52 to 0.96 liters/h/kg), the median t 1/2 α was 0.43 h (IQR, 0.05 to 1.82 h), and the median t 1/2 β was 233 h (IQR, 206 to 298 h). The noncompartmentally derived median DECQ t 1/2 β was 290 h (IQR, 236 to 368 h). Combined molar concentrations of DECQ and CQ were higher than those of PQ during the elimination phase. Although PQ has a longer t 1/2 β than CQ, its prompt distribution and lack of active metabolite may limit its posttreatment malaria-suppressive properties.

scholarly journals Erythropoietin kinetics in rats: generation and clearance

Blood ◽  
1986 ◽  
Vol 67 (3) ◽  
pp. 646-649
Author(s):  
SE Steinberg ◽  
JF Garcia ◽  
GR Matzke ◽  
J Mladenovic
Keyword(s):  
Intravenous Injection ◽  
Plasma Volume ◽  
Rat Model ◽  
Clearance Rate ◽  
Half Life ◽  
Plasma Clearance ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Two Compartment Model ◽  
Disappearance Curve

Detailed studies to analyze the early events of erythropoietin (Ep) secretion and clearance were performed in a rat model using a double antibody radioimmunoassay. Ep clearance was determined following intravenous injection of 1 mL of Ep-rich plasma, 1,080 mU/mL, obtained from phlebotomized rats. Analysis revealed a disappearance curve that conformed to a two-compartment model with an alpha half-life t1/2 of 3.6 minutes and a beta t1/2 of 86 minutes. The volume of distribution was similar to the calculated plasma volume. In anephric animals, there was no change in the plasma clearance rate or the volume of distribution. Rapid Ep secretion was elicited by a single 15 mL/kg phlebotomy (hematocrit decrement 45% to 30%), so that levels reached 20 to 30 times baseline (524 +/- 76 v 24 +/- 7 mU/mL) at five hours, whereas they plateaued for at least 33 hours. The increase in the rate of secretion was geometric, from 9.9 mU/h baseline secretion to 429 mU/h. These data identify a very sensitive and rapidly responsive system for Ep modulation in the rat.

scholarly journals The determination of thiocyanate in the blood plasma and holding water of Amphiprion clarkii after exposure to cyanide

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12409
Author(s):  
J. Alexander Bonanno ◽  
Nancy E. Breen ◽  
Michael F. Tlusty ◽  
Lawrence Andrade ◽  
Andrew L. Rhyne
Keyword(s):  
Blood Plasma ◽  
Plasma Levels ◽  
Half Life ◽  
Chronic Exposure ◽  
Compartment Model ◽  
The Body ◽  
Two Compartment Model ◽  
Low Levels ◽  
Amphiprion Clarkii

The illegal practice of cyanide fishing continues throughout the Indo-Pacific. To combat this destructive fishing method, a reliable test to detect whether a fish has been captured using cyanide (CN) is needed. We report on the toxicokinetics of acute, pulsed CN exposure and chronic thiocyanate (SCN) exposure, the major metabolite of CN, in the clownfish species, Amphiprion clarkii. Fish were pulse exposed to 50 ppm CN for 20 or 45 s or chronically exposed to 100 ppm SCN for 12 days and blood plasma levels of SCN were measured. SCN blood plasma levels reached a maximum concentration (301–468 ppb) 0.13–0.17 days after exposure to CN and had a 0.1 to 1.2 day half-life. The half-life of blood plasma SCN after chronic exposure to SCN was found to be 0.13 days. Interestingly, we observed that when a fish, with no previous CN or SCN exposure, was placed in holding water spiked to 20 ppb SCN, there was a steady decrease in the SCN concentration in the holding water until it could no longer be detected at 24 hrs. Under chronic exposure conditions (100 ppm, 12 days), trace levels of SCN (∼40 ppb) were detected in the holding water during depuration but decreased to below detection within the first 24 hrs. Our holding water experiments demonstrate that low levels of SCN in the holding water of A. clarkii will not persist, but rather will quickly and steadily decrease to below detection limits refuting several publications. After CN exposure, A. clarkii exhibits a classic two compartment model where SCN is eliminated from the blood plasma and is likely distributed throughout the body. Similar studies of other species must be examined to continue to develop our understanding of CN metabolism in marine fish before a reliable cyanide detection test can be developed.

Withdrawal of cefoperazone with milk after intramammary administration in dairy cows – prospective and retrospective analysis

2017 ◽  
Vol 20 (2) ◽  
pp. 261-268
Author(s):  
A. Burmańczuk ◽  
T. Grabowski ◽  
T. Błądek ◽  
C. Kowalski ◽  
P. Dębiak
Keyword(s):  
Dairy Cows ◽  
Half Life ◽  
Drug Distribution ◽  
Compartment Model ◽  
Clinical Mastitis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Lactation Period ◽  
Milk Samples ◽  
Drug Concentrations

Abstract The aim of the study was to carry out retrospective and prospective comparative analyses of the pharmacokinetics of CEF after single intramammary (IMM) administration in cows. The prospective study (study A) was conducted on 9 dairy cows of the Polish Black-White race with clinical mastitis during the lactation period. Milk samples were collected at 2, 4, 6, 8, 10, 24, 36, 48, 72 and 84 h after single IMM administration of 250 mg of CEF to one quarter. Drug concentrations in milk samples were determined by HPLC-MS/MS technique and the results of the pharmacokinetic analysis were compared to those obtained in previous studies based on the microbiological (study B) and HPLC-UV methods (study C and D). Pharmacokinetic parameters were calculated based on adapted two-compartment model of drug distribution. One of the findings of the comparison of the analysed investigations is that the CEF kinetics determined with the microbiological method is consistent with the results obtained by the authors of this paper. Both studies yielded similar results of the key pharmacokinetic parameters related to the level of the drug distribution to tissues and elimination half-life. In the pharmacodynamic analysis, the observations in all four studies were entirely consistent and have shown lower values of T>MIC90 in healthy animals and significantly higher values in infected dairy cows. The comparison of studies A, B, C, and D revealed that the time of complete CEF wash-out of 90.90% varied and amounted to 5.7, 8.0, 2.2, and 2.2 days after administration of the drug, respectively. It was confirmed that not only the type of the analytical method but also correct sampling have a significant impact on determination of the correct value of the drug half-life after IMM administration. The comparative analysis of studies in which the milk yield was high and low allows a conclusion that this parameter in the case of CEF has no significant effect on T>MIC90.

scholarly journals Population Pharmacokinetic Analysis of Voriconazole and Anidulafungin in Adult Patients with Invasive Aspergillosis

2014 ◽  
Vol 58 (8) ◽  
pp. 4718-4726 ◽  
Author(s):  
Ping Liu ◽  
Diane R. Mould
Keyword(s):  
Invasive Aspergillosis ◽  
Area Under The Curve ◽  
Compartment Model ◽  
Population Pharmacokinetic Analysis ◽  
Institutional Review Boards ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
First Order ◽  
Two Compartment Model

ABSTRACTTo assess the pharmacokinetics (PK) of voriconazole and anidulafungin in patients with invasive aspergillosis (IA) in comparison with other populations, sparse PK data were obtained for 305 adults from a prospective phase 3 study comparing voriconazole and anidulafungin in combination versus voriconazole monotherapy (voriconazole, 6 mg/kg intravenously [IV] every 12 h [q12h] for 24 h followed by 4 mg/kg IV q12h, switched to 300 mg orally q12h as appropriate; with placebo or anidulafungin IV, a 200-mg loading dose followed by 100 mg q24h). Voriconazole PK was described by a two-compartment model with first-order absorption and mixed linear and time-dependent nonlinear (Michaelis-Menten) elimination; anidulafungin PK was described by a two-compartment model with first-order elimination. For voriconazole, the normal inverse Wishart prior approach was implemented to stabilize the model. Compared to previous models, no new covariates were identified for voriconazole or anidulafungin. PK parameter estimates of voriconazole and anidulafungin are in agreement with those reported previously except for voriconazole clearance (the nonlinear clearance component became minimal). At a 4-mg/kg IV dose, voriconazole exposure tended to increase slightly as age, weight, or body mass index increased, but the difference was not considered clinically relevant. Estimated voriconazole exposures in IA patients at 4 mg/kg IV were higher than those reported for healthy adults (e.g., the average area under the curve over a 12-hour dosing interval [AUC0–12] at steady state was 46% higher); while it is not definitive, age and concomitant medications may impact this difference. Estimated anidulafungin exposures in IA patients were comparable to those reported for the general patient population. This study was approved by the appropriate institutional review boards or ethics committees and registered on ClinicalTrials.gov (NCT00531479).

Experimental validation of measurements of glucose turnover in nonsteady state.

1978 ◽  
Vol 234 (1) ◽  
pp. E84 ◽  
Author(s):  
J Radziuk ◽  
K H Norwich ◽  
M Vranic
Keyword(s):  
Dispersion Model ◽  
Glucose Production ◽  
Compartment Model ◽  
Sole Source ◽  
Volume Of Distribution ◽  
Endogenous Glucose Production ◽  
The Body ◽  
Glucose Turnover ◽  
Turnover Rates ◽  
Nonsteady State

The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.

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