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V Tammara

Publications and source records attributed to V Tammara.

5 recordsLinked to original sources
PubMed2004

A comparison of two sparse sampling population pharmacokinetic approaches for the estimation of pharmacokinetic parameters in children.

BACKGROUND AND OBJECTIVE: The objectives of this study were to assess pharmacokinetic parameters (clearance, volume and half-life) in children using sparse sampling population as well as Bayesian (post hoc) approach. METHODS: Three drugs were selected for this study. Two sparse sampling methods (variable or fixed) using population and Bayesian approaches were used to assess pharmacokinetic parameters in children following a single oral dose. The initial estimates of the model parameters and inter- and intrasubject variability were obtained from the pharmacokinetic studies conducted in adults. The estimated pharmacokinetic parameters using sparse sampling (3 blood samples) were compared with the pharmacokinetic parameters obtained by extensive sampling (> or = 7 blood samples). RESULTS AND CONCLUSIONS: The results indicated that both variable and fixed sampling approaches could be used to estimate mean population as well as individual pharmacokinetic parameters in children with fair degree of accuracy. The methods described here can be used to assess either population or individual pharmacokinetic parameters in children, provided there is a prior knowledge of the pharmacokinetics of a drug in adult population.

Adult↗
PubMed2001

Pharmacokinetic-pharmacodynamic modeling of rivastigmine, a cholinesterase inhibitor, in patients with Alzheimer's disease.

Rivastigmine is a cholinersterase inhibitor approved recently for the treatment of Alzheimer's disease (AD). The objective of this study is to characterize the pharmacokinetics-pharmacodynamics of rivastigmine in patients with AD. Eighteen AD patients received doses ranging from 1 to 6 mg bid for about 11 weeks. Rivastigmine and its active (major) metabolite (ZNS 114-666, also called NAP 226-90), plasma, and cerebrospinal fluid (CSF) concentrations were determined together with the AChE activity and computerized neuropsychological test battery (CNTB) scores. Nonlinear mixed-effects modeling of pharmacokinetic and pharmacodynamic data was conducted using NONMEM. Rivastigmine and its metabolite exhibited dose-disproportional pharmacokinetics. The apparent clearance and volume of distribution (plasma) of rivastigmine were estimated to be 120 L/h and 236 L, respectively. The relative bioavailability at the 6 mg dose was about 140%. The metabolite had a clearance of about 100 L/h and a volume of distribution of 256 L. The kinetics of the parent and metabolite in CSF showed an equilibration half-life of about 0.2 and 0.5 hours, respectively. The metabolite levels in CSF correlated very well with the acetylcholinesterase inhibition, with a ZNS 114-666 concentration of about 5.4 microg/L required for half-maximal inhibition of acetylcholinesterase activity. No statistically significant correlation of the CNTB scores with enzyme inhibition, parent or metabolite concentration (plasma/CSF), or rivastigmine dose could be established. The PK-PD model presented in this study can provide valuable information to optimize the drug development of rivastigmine and other related compounds and also in rationalizing dosing recommendations.

Acetylcholinesterase↗
PubMed1997

A limited sampling method for the estimation of vigabatrin maximum plasma concentration and area under the curve.

A limited sampling model (LSM) was developed to estimate the area under the curve (AUC) and maximum plasma concentration (Cmax) for a 1-g oral dose of vigabatrin. The model was developed using the data from 10 healthy subjects and one time point. The following equations describe the model for AUC and Cmax: AUC(predicted) = 5.4 x C3h + 70 and Cmax(predicted) = 0.18 x AUC(0-infinity) + 9.4. The model was validated in 49 subjects who orally received 1-g vigabatrin. This LSM was also used to predict AUC and Cmax volunteers who received 2- and 4-g vigabatrin doses and in renal failure patients who were given a 0.75-g dose. The model provided good estimates of both AUC and Cmax in all groups of subjects except renal dysfunction patients. The method described here may be used to estimate AUC and Cmax of vigabatrin without detailed pharmacokinetic studies.

Anticonvulsants↗
PubMed1997

A limited sampling approach in bioequivalence studies.

A limited sampling model (LSM) has been developed for an antidepressant immediate-release product (Drug A) and an antiepileptic controlled release product (Drug B) to predict the area under the curve (AUC) and the maximum plasma concentration (Cmax) and to compare the bioequivalence of two formulations of each drug using predicted versus observed AUC and Cmax after a single oral dose. The LSM for drug A was developed using data from 10 healthy people. The correlation between plasma concentration (independent variable) at selected time points with the AUC or Cmax (dependent variable) was evaluated by simple regression analysis. The linear regression that gave the best correlation coefficient (r) for a single sampling time versus AUC or Cmax was chosen as the LSM. The model provided good estimates of AUC and Cmax for drug A. The 90% confidence interval on log transformed observed and predicted AUC and Cmax were as follows: AUC observed = 100% to 118%, AUC predicted = 101% to 117%, Cmax observed = 99% to 125%, and Cmax predicted = 100% to 131%. The LSM for drug B was developed using a similar approach to drug A. The 90% confidence interval on log transformed observed and predicted AUC and Cmax were: AUC observed = 99% to 110%, AUC predicted = 99% to 118%, Cmax observed = 107% to 120%, and Cmax predicted = 99% to 111%. Although the predicted Cmax did not meet the 90% confidence interval for drug A, the method described here may be used to estimate AUC and Cmax for a drug in bioequivalence studies without detailed blood sampling. More research is needed in this direction.

Anticonvulsants↗