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Pharmacokinetics and Pharmacodynamics of Drugs Delivered to the Lung
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Stefanie K. Drescher, Mong-Jen Chen, Jürgen B. Bulitta, Günther Hochhaus
A much more robust parameter than tmax seems to be the estimation of the mean absorption time. This parameter can be readily calculated via non-compartmental analysis by estimating the mean residence time after inhalation (MRTinh) and subtracting the mean residence time after iv administration (MRTiv). This approach is relatively robust, as long as the terminal half-life can be reliably determined. Also, the mean absorption time allows one to characterize the absorption processes among different drugs if iv data are available. For example, differences in the absorption profiles between fluticasone propionate and budesonide can be easily identified with this method, while differences in tmax were not able to readily provide this information. The mean residence time without availability of intravenous data should not be used to compare absorption profiles of different drug entities, as it is also determined by the systemic elimination of the drug. The use of the mean residence time is, however, suitable for evaluating the differences in absorption of different formulations of the same drug.
Melarsoprol
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
A study by the same authors in uninfected monkeys supported the observations made in humans (Burri et al., 1994). Basic pharmacokinetic parameters determined included the mean residence time in serum of 18 hours, a volume of distribution of 3.6 l/kg, and a clearance of 3.5 ml/min/kg. The pharmacokinetic parameters achieved in serum and CSF were measured using two drug regimens—the original empirical schedule (WHO, 1986) and the alternate schedule (Burri et al., 1993). Serum levels of melarsoprol were calculated to decrease to very low levels between cycles in the empirical schedule, whereas a moderate level was maintained during a treatment course using the alternate schedule. This observation has been continued in a human study, where levels decreased to almost zero between treatment series (Burri et al., 1993).
In vitro and in vivo evaluation of a sustained-release once-a-day formulation of the novel antihypertensive drug MT-1207
Published in Pharmaceutical Development and Technology, 2021
Napoleon-Nikolaos Vrettos, Peng Wang, Yan Zhou, Clive J. Roberts, Jinyi Xu, Hong Yao, Zheying Zhu
The distribution of MT-1207 in the body is an important parameter considered during pharmacokinetic analysis. The apparent volume of distribution, Vd, reflects the space of the body seemed to be occupied by the drug (Shargel et al. 2012). Vd increases with increasing distribution of the drug to peripheral tissues. The mean residence time, MRT, reflects the average time during which the drug resides in the body. In the present case, even though the SR tablet showed the highest value for the apparent volume of distribution which was about 2.5 times higher than the IR tablet, there seemed to be no statistically significant difference (one-way ANOVA, p > 0.05) between the Vd values of MT-1207 recorded in SR o.d., IR t.i.d. and 3 × IR o.d (Table 3). Furthermore, with regards to MRT, the value obtained for 3 × IR o.d. increased more than 2 times for the same dose of MT-1207 administered as a sustained-release tablet (Table 3) and the difference between the two values was deemed to be statistically significant (t-test, p < 0.05). This indicates that the time during which the drug resides in the body was increased significantly when MT-1207 was administered in the form of a sustained-release tablet, compared to immediate-release tablets. There was a statistically significant difference in MRT between all three groups (one-way ANOVA, p < 0.05).
A novel combination of Soluplus®/Poloxamer for Meloxicam solid dispersions via hot melt extrusion for rapid onset of action. Part 2: comparative bioavailability and IVIVC
Published in Drug Development and Industrial Pharmacy, 2020
Nesrin F. Taha, Maha F. Emam, Laila H. Emara
Pharmacokinetic analysis: PK parameters for MLX were determined from the plasma concentration–time data by means of a noncompartmental analysis using the WinNonLin – Professional 2.1 (WNL-Pro 2.1) computer program (Pharsight, Mountain View, CA). The following parameters were evaluated: AUC0–96 (μg.h/mL) determined as the area under the plasma concentration–time curve up to the last measured sampling time and calculated by the trapezoidal rule; AUC0–∞ is the sum of AUC0–96, plus the residual area calculated as the concentration at the last measured time point divided by Kel (h−1). Kel is the elimination first order rate constant associated with the terminal (log-linear) portion of the curve. The maximum drug concentration (Cmax, μg/mL) and the time to reach Cmax (Tmax, h) were obtained from the individual plasma concentration–time curves. Mean residence time (MRT) (h) was calculated as AUMC/AUC, where AUMC is the area under the first moment of the drug concentration in blood or plasma curve [61]. The Wagner-Nelson (WN) method was used to calculate the fraction of MLX absorbed in vivo [62]: Ct represents the concentration at any time point.
Sulpiride gastro-retentive floating microsponges; analytical study, in vitro optimization and in vivo characterization
Published in Journal of Drug Targeting, 2020
Mahmoud A. Younis, Marwa R. El-Zahry, Mahmoud A. Tallat, Hesham M. Tawfeek
SUL plasma concentration versus time curve was plotted and the pharmacokinetics were calculated as previously reported [1,6,33]. Cmax and Tmax were directly-determined from the curve. The method of residual was adapted to obtain the rate constant of absorption (Kabs). The slope of the terminal linear portion of the curve was used to calculate the elimination rate constant (Kel.) from the linear regression analysis. The apparent half-lives of absorption and elimination (t½) were obtained via dividing 0.693 by the corresponding rate constant. Furthermore, the area under plasma concentration-time curve from zero to end time (AUC0–t) and the area under first moment curve from zero to end time (AUMC0–t) were calculated using linear trapezoidal rule. AUC and AUMC from zero-time to infinity (AUC0–∞ and AUMC0–∞) were calculated by Equations 3 and 4, respectively. t is the last measurable concentration at the end time point (t), Kel. is the elimination rate constant of drug. The mean residence time of the drug in the body (MRT) was calculated using Equation (5).