scholarly journals Is Dosing of Ethambutol as Part of a Fixed-Dose Combination Product Optimal for Mechanically Ventilated ICU Patients with Tuberculosis? A Population Pharmacokinetic Study

Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1559
Author(s):  
Francisco Beraldi-Magalhaes ◽  
Suzanne L. Parker ◽  
Cristina Sanches ◽  
Leandro Sousa Garcia ◽  
Brenda Karoline Souza Carvalho ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Oral Absorption ◽  
Compartment Model ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Population Pharmacokinetic ◽  
Icu Patients ◽  
Population Pharmacokinetic Study ◽  
Dosing Regimens ◽  
Dose Combination

Background: Tuberculosis (TB) patients admitted to intensive care units (ICU) have high mortality rates. It is uncertain whether the pharmacokinetics of first-line TB drugs in ICU patients are different from outpatients. This study aims to compare the pharmacokinetics of oral ethambutol in TB patients in ICU versus TB outpatients and to determine whether contemporary dosing regimens achieve therapeutic exposures. Methods: A prospective population pharmacokinetic study of ethambutol was performed in Amazonas State, Brazil. Probability of target attainment was determined using AUC/MIC > 11.9 and Cmax/MIC > 0.48 values. Optimized dosing regimens were simulated at steady state. Results: Ten ICU patients and 20 outpatients were recruited. Ethambutol pharmacokinetics were best described using a two-compartment model with first-order oral absorption. Neither ICU patients nor outpatients consistently achieved optimal ethambutol exposures. The absorption rate for ethambutol was 2-times higher in ICU patients (p < 0.05). Mean bioavailability for ICU patients was >5-times higher than outpatients (p < 0.0001). Clearance and volume of distribution were 93% (p < 0.0001) and 53% (p = 0.002) lower in ICU patients, respectively. Conclusions: ICU patients displayed significantly different pharmacokinetics for an oral fixed-dose combination administration of ethambutol compared to outpatients, and neither patient group consistently achieved pre-defined therapeutic exposures.

scholarly journals Population Pharmacokinetic Study of Cefathiamidine in Infants With Augmented Renal Clearance

2021 ◽  
Vol 12 ◽  
Author(s):  
Bin Du ◽  
Yue Zhou ◽  
Bo-Hao Tang ◽  
Yue-E Wu ◽  
Xin-Mei Yang ◽  
...  
Keyword(s):  
Renal Clearance ◽  
Pharmacokinetic Study ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Studies ◽  
Augmented Renal Clearance ◽  
Population Pharmacokinetic Study ◽  
Dosing Regimens

Objectives: Augmented renal clearance (ARC) of primarily renally eliminated antibacterial agents may result in subtherapeutic antibiotic concentrations and, as a consequence, worse clinical outcomes. Cefathiamidine is frequently used as empirical antimicrobial therapy in children with ARC, but pharmacokinetic studies in infants are lacking. This population pharmacokinetic study in infants with ARC was conducted to determine optimal dosing regimens of cefathiamidine.Methods: The population pharmacokinetics was conducted in 20 infants treated with cefathiamidine. Plasma samples of cefathiamidine were collected using opportunistic sampling, and the concentrations were detected by UPLC-MS/MS. Data analysis was performed to determine pharmacokinetic parameters and to characterize pharmacokinetic variability of cefathiamidine using nonlinear mixed effects modelling (NONMEM) software program.Results: The data (n = 36) from 20 infants (age range, 0.35–1.86 years) with ARC were fitted best with a 1-compartment model. Allometrically scaled weight and age as significant covariates influenced cefathiamidine pharmacokinetics. The median (range) values of estimated clearance and the volume of distribution were 0.22 (0.09–0.29) L/h/kg and 0.34 (0.24–0.41) L/kg, respectively. Monte Carlo simulations showed that the cefathiamidine doses of 100 mg/kg/day q12 h, 50 mg/kg/day q8 h and 75 mg/kg/day q6 h were chosen for bacteria with MIC 0.25, 0.5 and 2 mg/L, respectively.Conclusion: The population pharmacokinetic model of cefathiamidine for infants with ARC was developed. The PTA - based dosing regimens were recommended based on the final model.

scholarly journals Simultaneous Determination of a Fixed-Dose Combination of Lercanidipine and Valsartan in Human Plasma by LC–MS-MS: Application to a Pharmacokinetic Study

2016 ◽  
Vol 54 (9) ◽  
pp. 1553-1559 ◽  
Author(s):  
Eboka Majolene B. Sabi-mouka ◽  
Janvier Engelbert Agbokponto ◽  
Run Zhang ◽  
Qian Li ◽  
Li Ding
Keyword(s):  
Simultaneous Determination ◽  
Human Plasma ◽  
Pharmacokinetic Study ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Dose Combination

scholarly journals Pharmacokinetic study of metformin to compare voglibose/metformin fixed-dose combination with coadministered voglibose and metformin

2015 ◽  
Vol 53 (02) ◽  
pp. 147-153 ◽  
Author(s):  
Hyang-Ki Choi ◽  
Minkyung Oh ◽  
Eun Ji Kim ◽  
Geun Seog Song ◽  
Jong-lyul Ghim ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Dose Combination

A New Fixed-Dose Combination for Added Blood Pressure Control: Telmisartan Plus Hydrochlorothiazide

2002 ◽  
Vol 30 (4) ◽  
pp. 366-379 ◽  
Author(s):  
Y Lacourcière
Keyword(s):  
Blood Pressure ◽  
Cost Effective ◽  
Pressure Control ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Angiotensin Ii Receptor Blocker ◽  
Angiotensin Ii Receptor ◽  
Wide Range ◽  
Dosing Regimens ◽  
Dose Combination

Population surveys on hypertension management reveal worrying deficiencies in the awareness and treatment of high blood pressure. Many patients with hypertension will require two or more drugs with complementary mechanisms of action (which generally have additive effects, producing greater blood pressure reductions than either agent alone) to attain the blood pressure goals specified in internationally accepted guidelines. Nevertheless, physicians are often reluctant to prescribe multiple anti-hypertensive drugs due to concerns over side-effects, inconvenient dosing regimens and costs. Fixed-dose formulations combining two agents from different classes in a single tablet should help to allay these concerns. A fixed-dose combination containing telmisartan (an angiotensin II receptor blocker) and hydrochlorothiazide (a thiazide diuretic) has recently been developed. Telmisartan/hydrochlorothiazide provides additional anti-hypertensive efficacy compared with the respective monotherapies in a wide range of patients, including black patients, requires once-daily dosing, is cost-effective, well tolerated and is associated with less potassium depletion than hydrochlorothiazide administered alone.

scholarly journals Population Pharmacokinetics and Pharmacodynamic Considerations of Amodiaquine and Desethylamodiaquine in Kenyan Adults with Uncomplicated Malaria Receiving Artesunate-Amodiaquine Combination Therapy

2010 ◽  
Vol 54 (6) ◽  
pp. 2611-2617 ◽  
Author(s):  
Vincent Jullien ◽  
Bernhards Ogutu ◽  
Elizabeth Juma ◽  
Gwenaelle Carn ◽  
Charles Obonyo ◽  
...  
Keyword(s):  
Uncomplicated Malaria ◽  
Elimination Rate ◽  
Parasite Clearance ◽  
Compartment Model ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
First Order ◽  
Dose Combination ◽  
The Mean

ABSTRACT Amodiaquine (AQ) is an antimalarial drug that was frequently combined with artesunate (AS) for the treatment of uncomplicated malaria due to Plasmodium falciparum and is now available as a fixed-dose combination. Despite its widespread use, the simultaneous pharmacokinetics in patients of AQ and its active metabolite, desethylamodiaquine (DAQ), were not characterized to date. The pharmacokinetics of AQ and DAQ in 54 adult patients receiving the AS/AQ combination were therefore investigated by the use of a population approach. AQ followed a 1-compartment model with first-order absorption and elimination, as well as a first-order and irreversible transformation into DAQ, which in turn followed a 2-compartment model with first-order elimination from its central compartment. The mean AQ apparent clearance and distribution volume were 3,410 liters/h and 39,200 liters, respectively. The mean terminal elimination half-life of DAQ was 211 h. Body weight was found to explain the interindividual variability of the apparent volume of distribution of AQ and the elimination rate constant of DAQ. A new dosage form consisting of a fixed-dose combination of AS and AQ was found to have no effect on the pharmacokinetic parameters of AQ and DAQ. All patients achieved parasite clearance within 4 days following the initiation of the treatment, which prevented investigation of the possible relationship between DAQ exposure and treatment outcome. This study provided the first simultaneous pharmacokinetic model for AQ and DAQ.

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