Preliminary study of the association between the elimination parameters of phenytoin and phenobarbital

2017 ◽  
Vol 32 (3) ◽  
Author(s):  
Janthima Methaneethorn ◽  
Duangchit Panomvana ◽  
Thaveechai Vachirayonstien
Keyword(s):  
Steady State ◽  
Medical Records ◽  
Maximum Rate ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Regression Equations ◽  
Simple Linear Regression ◽  
Epileptic Patients ◽  
Preliminary Study ◽  
The Relationship

AbstractBackground:Therapeutic drug monitoring is essential for both phenytoin and phenobarbital therapy given their narrow therapeutic indexes. Nevertheless, the measurement of either phenytoin or phenobarbital concentrations might not be available in some rural hospitals. Information assisting individualized phenytoin and phenobarbital combination therapy is important. This study’s objective was to determine the relationship between the maximum rate of metabolism of phenytoin (VMethods:Data on phenytoin and phenobarbital concentrations of 19 epileptic patients concurrently receiving both drugs were obtained from medical records. Phenytoin and phenobarbital pharmacokinetic parameters were studied at steady-state conditions. The relationship between the elimination parameters of both drugs was determined using simple linear regression.Results:A high correlation coefficient between VConclusions:Regression equations were established for estimating V

scholarly journals Evaluating the Relationship between Vancomycin Trough Concentration and 24-Hour Area under the Concentration-Time Curve in Neonates

2018 ◽  
Vol 62 (4) ◽  
pp. e01647-17 ◽  
Author(s):  
Sheng-Hsuan Tseng ◽  
Chuan Poh Lim ◽  
Qi Chen ◽  
Cheng Cai Tang ◽  
Sing Teang Kong ◽  
...  
Keyword(s):  
Steady State ◽  
Trough Concentration ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
Vancomycin Trough ◽  
Trough Concentrations ◽  
The Relationship

ABSTRACT Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant Staphylococcus aureus (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC24/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC24 values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC24. A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC24/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC24/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.

scholarly journals The Pharmacokinetic Study of Progesterone and Allopregnanolone in Refractory Epilepsy : Phase II Study

2021 ◽  
Author(s):  
Marisa Senngam ◽  
Juthathip Suphanklang ◽  
Wichai santimaleeworagun ◽  
Piradee Suwanpakdee ◽  
Pornsawan Mekhasingharrak ◽  
...  
Keyword(s):  
Seizure Frequency ◽  
Maximum Concentration ◽  
Refractory Epilepsy ◽  
Serum Levels ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Serum Progesterone ◽  
Minimum Concentration ◽  
Clinical Trials Registry ◽  
The Relationship

Abstract Background: Progesterone belongs to a class of neurosteroids used for the reduction of seizure frequency in patients with refractory epilepsy. However, the pharmacokinetics of progesterone and its active derivative, allopregnanolone, have never been studied in these patients. Objectives: This study was aim to explore the pharmacokinetic parameters of progesterone 400 mg every 12 h, for 3 months, in patients with refractory epilepsy as an add-on therapy to control seizures. Phoenix® WinNonlin® was used to analyse the pharmacokinetic parameters. Results: Twelve patients were recruited. From a therapeutic drug monitoring, the serum progesterone and allopregnanolone levels after taking the first dose of progesterone were characterised by a time to maximum concentration (Tmax) median of 1 and 2.5 h, a maximum concentration (Cmax) median of 274.97 and 3.81 ng/mL, and a minimum concentration (Cmin) median of 56.93 and 1.06 ng/mL, respectively. The median values of the pharmacokinetic parameters of progesterone and allopregnanolone during the steady state were as follows: t1/2 of 2.4 and 2.0 h, Cmax of 964.35 and 8.92 ng/mL, and Cmin of 64.67 and 1.86 ng/mL, respectively. By examining the relationship between the progesterone or allopregnanolone concentrations with seizure-controlling ability, we could identify a responder patient group with 6- to 7-fold higher serum concentrations of progesterone and allopregnanolone than the non-responders. Conclusions: We could establish higher serum levels of both progesterone and allopregnanolone, which could consequently relate to lowering the seizure frequency in patients with refractory epilepsy. The suggested progesterone dose was 400 mg orally every 12 h against refractory epilepsy Trial registration: This study has been registered on the Thai Clinical Trials Registry (No. TCTR20200710005, 10 July 2020)

DETERMINATION OF PHARMACOKINETIC PARAMETERS AND FACTORS INFLUENCING THE PHARMACOKINETIC PARAMETERS OF PHENYTOIN IN THAI CHILDREN WITH EPILEPSY

2021 ◽  
pp. 47-51
Author(s):  
CHANRUANG A. ◽  
RAKNGAM M. ◽  
TEEKACHUNHATEAN S. ◽  
DAENGSUEPTRAKUN K. ◽  
PUNYAWUDHO B.
Keyword(s):  
Steady State ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Metabolizing Enzymes ◽  
Linear Mixed Effects ◽  
Factors Influencing ◽  
Patients With Epilepsy ◽  
State Concentration

Objective: Phenytoin displays nonlinear pharmacokinetics due to the saturation of its’ metabolizing enzymes, thus making dosing adjustments a challenge in clinical practice. However, data on the pharmacokinetic parameters of phenytoin in pediatric patients with epilepsy in Thailand remain lacking. This study aimed to determine the pharmacokinetic parameters of phenytoin, and the factors influencing them in epileptic Thai children using therapeutic drug monitoring data. Methods: Steady state phenytoin plasma concentrations were collected from 96 Thai children with epilepsy aged ≤ 15 y. For individuals having a single steady-state concentration (Css) on one dosage, the Vmax was determined by fixing Km = 4.5 mg/l. For patients with two values for Css with different dosages, the Ludden method was used to determine Vmax and Km. Influences on Vmax and Km by demographic factors including age, sex, weight, serum albumin, and the use of CYP2C9 inducers (carbamazepine, phenobarbital, folic acid, and vigabatrin) and inhibitors (valproic acid and topiramate) were determined by linear mixed-effects regression. Results: The majority of patients had sub-therapeutic plasma concentrations of phenytoin. The Vmax and Km were estimated to be 9.84 mg/kg/d and 2.32 mg/l, respectively. Age and weight significantly influenced Vmax, whereas Km had no significant influencing factors. Conclusion: The Vmax estimated in this study is different from other populations previously reported. Our results suggest that increased phenytoin dosages may be required to achieve optimal concentrations due to the sub-therapeutic concentrations reported here. The results from this study are beneficial for phenytoin dosage individualization in Thai children.

Pharmacokinetic and pharmacodynamic analysis of fluorouracil in nasopharyngeal cancer patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13021-e13021
Author(s):  
Liping Zhao ◽  
Wanli Liu ◽  
Chong Zhao ◽  
Xiang Guo ◽  
Yan Huang ◽  
...  
Keyword(s):  
Steady State ◽  
Nasopharyngeal Cancer ◽  
Target Range ◽  
Therapeutic Drug ◽  
Severe Toxicity ◽  
Pharmacodynamic Analysis ◽  
Treatment Naïve ◽  
Tumor Types ◽  
The Relationship ◽  
Severe Mucositis

e13021 Background: Pharmacokinetic (PK) variability of 5-FU has been demonstrated for +30 years and a significant link between 5-FU exposure and therapeutic response has been identified. A maximum tolerated exposure (MTE) using area under curve (AUC) has been characterized for various regimens and therapeutic drug management (TDM) has been used to achieve effective dosing in several tumor types. The regimen most used to treat nasopharyngeal cancer (NPC) is cisplatin and 5-FU. The objective of this study was to characterize the PK variability of 5-FU in this population and examine the relationship between AUC and toxicity. The 5-FU MTE in this Chinese population will be compared with the MTE identified for HNC European patients. Methods: Fifty-three treatment naïve Chinese NPC patients were administered cisplatin (80mg/m2, day 1) and 5-FU (4g/m2, 120 h continuous infusion) and had blood samples collected at steady state after the first 18h of 5-FU infusion. Plasma was analyzed by a 5-FU immunoassay and AUC calculated from the steady state concentrations. We examined the relationship between 5-FU AUC and 5-FU-related toxicities (mucositis and myelosuppression). Results: The patient AUC values varied widely, ranging from 20 to 103 mg · h/L. 34% of the patients were within the target range of 25-35 mg· h/L , 15% were below and 51% were above the range. Toxicity was recorded for 53 patients. Severe mucositis in 17 and myelosuppression in 1 of 27 patients occurred with 5-FU exposure above the target range, versus no severe toxicity in any of the 27 patients within or below the target range (p=0.000). ROC analysis for 5-FU AUC and severe mucositis identified a cut-point of 37 mg· h/L (p<0.001). Conclusions: Results of this study demonstrate wide PK-variability of 5-FU exposure and a significant relationship between severe toxicity and AUC in Chinese NPC patients. The study confirms that the MTE in this population is similar to a European HNC population treated with cisplatin/5-FU. TDM using the target range of 25-35 mg· h/L may have benefit in lowering toxicity in NPC patients.

scholarly journals The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients

2017 ◽  
Vol 2 ◽  
pp. 353-360 ◽  
Author(s):  
Chahra Chbili ◽  
Anis Hassine ◽  
Aicha Laouani ◽  
Sana Ben Amor ◽  
Manel Nouira ◽  
...  
Keyword(s):  
Therapeutic Response ◽  
Pharmacokinetic Parameters ◽  
Epileptic Patients ◽  
The Relationship

Predictive Techniques Applied to Imipramine Therapeutic Drug Monitoring

DICP ◽  
1989 ◽  
Vol 23 (5) ◽  
pp. 389-394
Author(s):  
M. Mar Fernandez de Gatta ◽  
Milagros Tamayo ◽  
Maria José Garcia ◽  
Cristobal Montojo ◽  
J. Ramón Gutierrez ◽  
...  
Keyword(s):  
Steady State ◽  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Prediction Error ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Serum Concentrations ◽  
Drug Concentrations ◽  
Steady State Serum

The aim of this study was to establish the performance of pharmacokinetic methods employing little data on serum drug concentrations obtained in routine therapeutic drug monitoring of imipramine. Forty-three and 123 serum levels were obtained in 8 adult depressive patients (aged 57–80 y) and 34 enuretic children (aged 5–13 y), respectively. Forecasting of the serum concentrations was performed based on mean population pharmacokinetic parameters (method A), with knowledge of one steady-state serum concentration (method B), and from two or more steady-state serum concentrations (method C). The accuracy and precision of each method were evaluated from the mean prediction error (ME) and from the root mean squared prediction error (RMSE), respectively. The values of ME and RMSE of methods B and C proved to be significantly lower than those found using method A. Method C was the most precise and accurate in both populations. Method A underestimates the serum concentrations observed in adults (ME >0) but overestimates them in children (ME <0), although to a lesser extent. The study shows that it is possible to obtain a good estimation of individual dosage needs from one or more serum concentrations obtained at steady state. Clinical application of these methods (B and C) yields an increase in the efficiency and safety of the treatment, particularly in special populations such as geriatric and pediatric patients.

scholarly journals Serum Voriconazole Level Variability in Patients with Hematological Malignancies Receiving Voriconazole Therapy

2014 ◽  
Vol 25 (5) ◽  
pp. 271-276 ◽  
Author(s):  
Lalit Saini ◽  
Jack T Seki ◽  
Deepali Kumar ◽  
Eshetu G Atenafu ◽  
David EC Cole ◽  
...  
Keyword(s):  
Steady State ◽  
Acute Leukemia ◽  
Hematological Malignancies ◽  
Liver Toxicity ◽  
Serum Alkaline Phosphatase ◽  
Plasma Concentrations ◽  
Therapeutic Drug ◽  
Poor Correlation ◽  
Intensive Chemotherapy ◽  
The Relationship

INTRODUCTION: Voriconazole plasma concentrations have been correlated with oral dosing in healthy subjects, but have been poorly characterized in ill patients with hematological malignancies receiving intensive chemotherapy.METHODS: The relationship between orally administered voriconazole, plasma concentrations and liver toxicity was examined in a cohort of 69 primarily acute leukemia patients undergoing intensive chemotherapy.RESULTS: Oral administration of voriconazole was associated with significant interpatient variability, with voriconazole steady-state concentrations ranging from 0 μg/mL to 16.6 μg/mL. Approximately 20% of patients achieved steady-state concentrations <1 μg/mL. When adjusted for weight, patients receiving higher voriconazole doses tended toward higher plasma concentrations; however, there was no significant relationship between the plasma concentration and genotype, age, sex or use of concomitant proton pump inhibitors. Voriconazole concentrations were correlated with higher serum alkaline phosphatase levels at day 6 to 8, and with higher bilirubin and aspartate aminotransferase levels at day 14 to 16, but not with other liver enzyme levels.CONCLUSION: In ill patients with acute leukemia and related disorders undergoing treatment with oral voriconazole, there is a poor correlation between the voriconazole dose and plasma concentrations, and many patients achieve levels that are considered to be subtherapeutic. The findings support the routine use of therapeutic drug monitoring in these patients.

scholarly journals Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Xuemei Wu ◽  
Cornelius J. Clancy ◽  
Ryan M. Rivosecchi ◽  
Wenchen Zhao ◽  
Ryan K. Shields ◽  
...  
Keyword(s):  
Steady State ◽  
Plasma Concentration ◽  
Fungal Infections ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Interpatient Variability ◽  
Trough Plasma

ABSTRACT Isavuconazole may be useful in treating and preventing fungal infections in solid-organ transplant (SOT) recipients due to its safety profile and activity against Aspergillus and some Mucorales. Isavuconazole has favorable pharmacokinetics based on clinical trials in various patient populations, but data are limited in SOT recipients. We evaluated the steady-state pharmacokinetics of isavuconazole in 26 SOT recipients receiving the drug intravenously for prophylaxis. There was moderate interpatient variability in isavuconazole pharmacokinetic parameters (coefficients of variation of 51% for the area under the plasma concentration-versus-time curve [AUC] and 59% for the trough plasma concentration [Ctrough]). AUC and steady-state Ctrough were significantly lower in women, patients with a body mass index of ≥18.5 kg/m2, and those receiving hemodialysis. Trough plasma concentrations were highly correlated with AUCs (R2 = 0.94) and can serve as a suitable measure of isavuconazole exposure in patients. In conclusion, moderate interpatient variability in isavuconazole exposure, the identification of factors associated with lower exposure, the recognition that Ctrough is a surrogate marker for AUC, and the availability of a simple analytical method suggest that therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least some SOT recipients. Future studies are needed to correlate isavuconazole exposure with patients’ clinical outcomes and to determine the clinical role of TDM.

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