Pharmacokinetic compartment models are the only models that can extract pharmacokinetic parameters from data collected in clinical studies but their estimates lack accuracy, explanations and physiological significance...Pharmacokinetic compartment models are the only models that can extract pharmacokinetic parameters from data collected in clinical studies but their estimates lack accuracy, explanations and physiological significance. The objective of this work was to develop particular solutions to drug concentration and AUC in the form of mathematical series and Heaviside functions for repetitive intermittent infusions in the one- and two-compartment models, as a function of dose number and total time using differential calculus. It was demonstrated that the central and peripheral compartment volumes determined from regression analysis of the aminoglycoside antibiotic Sisomicin concentration in plasma represent the actual physiological body fluid volumes accessible by the drug. The drug peak time and peak concentration in the peripheral compartment were also calculated as a function of dose number. It is also shown that the time of intercompartmental momentary distribution equilibrium can be used to determine the drug’s apparent volume of distribution within any dosing interval in multi-compartment models. These estimates were used to carry out simulations of plasma drug concentration with time in the one-compartment model. In conclusion, the two-compartment open mammillary pharmacokinetic model was fully explained for the aminoglycoside antibiotic sisomicin through the new concept of the apparent volume of distribution.展开更多
Published clinical data of Prazosin were reevaluated pharmacokinetically using explicit solutions to drug concentration as a function of total time for IV bolus injection, intermittent intravenous infusion and oral ro...Published clinical data of Prazosin were reevaluated pharmacokinetically using explicit solutions to drug concentration as a function of total time for IV bolus injection, intermittent intravenous infusion and oral routes of administration in an open two-compartment model. In a novel way, the apparent volume of distribution was estimated from a two-compartment model and found to be close to the total body water suggesting that Prazosin is distributed in all tissues both extracellularly and intracellularly. In addition, extracting the value of the apparent volume of distribution from a two-compartment model allowed comparative simulations in the one-compartment model. It is shown that dosage calculations of Prazosin intermittent infusion can be safely performed using the simpler one-compartment model equations. Lastly, several additional time-dependent pharmacokinetic parameters e.g., the peak time in the central and peripheral compartment and non-steady state and steady state peak concentration and AUC were determined using series equations for all three routes of administration, as a function of dose number and total time upon multiple drug administrations in the two-compartment model. It is also the first time that steady-state plasma drug concentration equations were derived in a two-compartment mammillary model.展开更多
Background A new fluroquinolone antibacterial agent,antofloxacin hydrochloride,developed in China,is an 8-NH2 derivant of levofloxacin.The purpose of the study was to evaluate the pharmacokinetic characteristics of si...Background A new fluroquinolone antibacterial agent,antofloxacin hydrochloride,developed in China,is an 8-NH2 derivant of levofloxacin.The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.Methods An open-label,non-randomized,single and multiple dose clinical trial was conducted.In single dose study,12 subjects took 200 mg antofloxacin hydrochloride.In multiple dose study,12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7.HPLC was used to assay the serum and urinary concentrations of antofloxacin.Results In single dose study,the maximum concentration of drug in serum （Cmax）,the time to reach Cmax （Tmax）,and the area under the serum concentration-time curve （AUC （O-∞）） of antofloxacin were （1.89±0.65） mg/L,（1.29±0.26） hours,39.1%.In multiple dose study,blood concentration of antofloxiacin achieved stable state on day 2 after dosing.The minimum concentration drug in serum （Cmin）,AUCss,mean concentration of drug in serum （Cav）,and degree offluctuation （DF） were （0.73±0.18） mg/L, （47.59±7.85） mg·h^-1·L^-1, （1.98±0.33） mg/L, and 1.74±0.60, respectively. On day 7 after dosing, Tmax ,Cmax and AUC （0-∞） was （1.14±0.50） hours, （2.52±0.38） mg/L, and （48.77±8.44） mg·h^-1·L^-1, respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.Conclusions The regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.展开更多
文摘Pharmacokinetic compartment models are the only models that can extract pharmacokinetic parameters from data collected in clinical studies but their estimates lack accuracy, explanations and physiological significance. The objective of this work was to develop particular solutions to drug concentration and AUC in the form of mathematical series and Heaviside functions for repetitive intermittent infusions in the one- and two-compartment models, as a function of dose number and total time using differential calculus. It was demonstrated that the central and peripheral compartment volumes determined from regression analysis of the aminoglycoside antibiotic Sisomicin concentration in plasma represent the actual physiological body fluid volumes accessible by the drug. The drug peak time and peak concentration in the peripheral compartment were also calculated as a function of dose number. It is also shown that the time of intercompartmental momentary distribution equilibrium can be used to determine the drug’s apparent volume of distribution within any dosing interval in multi-compartment models. These estimates were used to carry out simulations of plasma drug concentration with time in the one-compartment model. In conclusion, the two-compartment open mammillary pharmacokinetic model was fully explained for the aminoglycoside antibiotic sisomicin through the new concept of the apparent volume of distribution.
文摘Published clinical data of Prazosin were reevaluated pharmacokinetically using explicit solutions to drug concentration as a function of total time for IV bolus injection, intermittent intravenous infusion and oral routes of administration in an open two-compartment model. In a novel way, the apparent volume of distribution was estimated from a two-compartment model and found to be close to the total body water suggesting that Prazosin is distributed in all tissues both extracellularly and intracellularly. In addition, extracting the value of the apparent volume of distribution from a two-compartment model allowed comparative simulations in the one-compartment model. It is shown that dosage calculations of Prazosin intermittent infusion can be safely performed using the simpler one-compartment model equations. Lastly, several additional time-dependent pharmacokinetic parameters e.g., the peak time in the central and peripheral compartment and non-steady state and steady state peak concentration and AUC were determined using series equations for all three routes of administration, as a function of dose number and total time upon multiple drug administrations in the two-compartment model. It is also the first time that steady-state plasma drug concentration equations were derived in a two-compartment mammillary model.
文摘Background A new fluroquinolone antibacterial agent,antofloxacin hydrochloride,developed in China,is an 8-NH2 derivant of levofloxacin.The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.Methods An open-label,non-randomized,single and multiple dose clinical trial was conducted.In single dose study,12 subjects took 200 mg antofloxacin hydrochloride.In multiple dose study,12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7.HPLC was used to assay the serum and urinary concentrations of antofloxacin.Results In single dose study,the maximum concentration of drug in serum （Cmax）,the time to reach Cmax （Tmax）,and the area under the serum concentration-time curve （AUC （O-∞）） of antofloxacin were （1.89±0.65） mg/L,（1.29±0.26） hours,39.1%.In multiple dose study,blood concentration of antofloxiacin achieved stable state on day 2 after dosing.The minimum concentration drug in serum （Cmin）,AUCss,mean concentration of drug in serum （Cav）,and degree offluctuation （DF） were （0.73±0.18） mg/L, （47.59±7.85） mg·h^-1·L^-1, （1.98±0.33） mg/L, and 1.74±0.60, respectively. On day 7 after dosing, Tmax ,Cmax and AUC （0-∞） was （1.14±0.50） hours, （2.52±0.38） mg/L, and （48.77±8.44） mg·h^-1·L^-1, respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.Conclusions The regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.
