ABSTRACT
This study is to develop a therapeutic drug monitoring (TDM) network server of tacrolimus for Chinese renal transplant patients, which can facilitate doctor to manage patients' information and provide three levels of predictions. Database management system MySQL was employed to build and manage the database of patients and doctors' information, and hypertext mark-up language (HTML) and Java server pages (JSP) technology were employed to construct network server for database management. Based on the population pharmacokinetic model of tacrolimus for Chinese renal transplant patients, above program languages were used to construct the population prediction and subpopulation prediction modules. Based on Bayesian principle and maximization of the posterior probability function, an objective function was established, and minimized by an optimization algorithm to estimate patient's individual pharmacokinetic parameters. It is proved that the network server has the basic functions for database management and three levels of prediction to aid doctor to optimize the regimen of tacrolimus for Chinese renal transplant patients.
ABSTRACT
Pharmacometrics,developed from the conventional pharmacokinetics,is the science of applying mathe-matical and statistical methods to characterize,understand,and predict a drug's pharmacokinetic,phannacodyna-mic,and biomarker-outcome behaviors.Pharmacometrics has been widely valued for its utility of modeling and simulation in drug research and development,therapeutic drug monitoring and individualized therapy.This paper reviewed the advances of pharmacometrics employed in new drug research and development and therapeutic drug monitoring both at home and abroad.
ABSTRACT
AIM: To determine the interactions with response-surface modeling methodologies when sevoflurane (Sevo) and remifentanil (Remi) were administered simultaneously. METHODS: (1) Patients, Study design and drug delivery: Based on parallel slices design, sixty-five patients were randomly assigned to inhale a specific end-tidal concentration of sevoflurane (0.3% to 3.4%), with different level of remifentanil (0-10 ng/mL). The responses to laryngoscopy were observed for each given concentration pair. (2) Pharmacokinetic/pharmacodynamic analysis with response surface mode: The probability of no response (P) was assessed in the modeling process as below. P=(Us+Ur)r/[U50/I(Q)]r+(Us+Ur)r RESULTS AND DISCUSSION: NONMEM estimated average values (RSE%) of the model parameters for laryngoscopy of C50,Sevo, C50,remi, U50, r, Imax and Qmax are 1.71% (12.9), 12.4 ng/mL (19.0), 6.62 (10.6), 1.53 (8.76), 2.31 (8.23), 0.706 (2.46), respectively. The inter-individual variability (CV%) in parameter Imax and inter-occasion variability (S.D.) in this model are 12.7 and 0.0316, respectively. It is concluded that the response-surface modeling approach provided a novel method to study drug-drug interactions.
ABSTRACT
Objective To investigate the pharmacodynamic interactions between remifentanil and sevoflurane during general anesthesia for laparoscopic operation.Methods Sixty-five ASA I patients undergoing selective laparoscopic operations at the Department of Gynecology and the Department of General Surgery in People's Hospital were enrolled in this study.Sevoflurane was used for anesthesia induction with its expired concentration being kept stable,and different dosages of remifentanil(0,1,2,4,6,and 8 ng/ml)being added during the operation.When the expired concentration of sevoflurane reached an expected level(pseuto-state),the block somatic and cardiovascular responses to electrical tetanus stimuli(ETS;100 Hz,60 mA,5 s)were measured.The data were analyzed using NONMEM software to establish concentration-effect curves.Logistic regression was used to calculate the minimal alveolar concentration of sevoflurane under ETS(MACETS).Results In the cases received sevoflurane only,the somatic response was inhibited when MACETS reached 1.52%;while the cardiovascular response was inhibited when MACETS reached 2.24%.The MACETS was decreased significantly by adding low-dosage remifentanil.When the target-controlled concentration of remifentanil was 8 ng/ml,the MACETS for the inhibition of somatic and cardiovascular responses decreased by 70.0% and 76.3%,respectively.Conclusions There is a synergic effect between remifentanil and sevoflurane on the suppression of somatic and cardiovascular responses to ETS.Remifentanil produces a dose-dependent decrease of MACETS of sevoflurane.The effect is especially strong in low-dosage remifentanil group,but shows ceiling effect characteristics.