Factors Affecting the Clinical Outcome of Aerosol Therapy
Hans Bisgaard, Chris O’Callaghan, Gerald C. Smaldone in Drug Delivery to the Lung, 2001
Increased potency has sometimes been claimed to be an advantage, as smaller amounts of drug will lead to a similar therapeutic effect. It should be emphasized that the maximal effect, elicited by inhaled β2-agonists or glucocorticosteroids, is not affected by the potency of the drug. Prolonged pulmonary retention of an inhaled drug, however, may represent an advantage, as is now clear from studies with long-acting β2-agonists in asthmatic patients (55). Although differences in lung retention between inhaled glucocorticosteroids appear to exist, the potential clinical relevance of this finding—less systemic exposure, reduced dosing frequency, and hence a better therapeutic compliance—remains to be investigated. Prolonged elimination half-life is, however, of some relevance, as it causes accumulation of the drug and may lead to measurable systemic effects. The clinical relevance of a measurable systemic effect, such as a suppression of adrenal function or an alteration in serum markers of bone metabolism, remains unknown. However, the relationship between a measurable systemic effect and the development of a clinically relevant side effect—such as cataract, osteoporosis, or reduced growth—remains to be established. In fact, only the relationship between inhaled glucocorticosteroids and skin thinning or easy bruising is generally accepted to be causal of nature (56,57).
Psychopharmacology EMIs
Michael Reilly, Bangaru Raju in Extended Matching Items for the MRCPsych Part 1, 2018
Active transport.Bioavailability.Bioequivalence.Blood–brain barrier.Elimination half-life.First-order kinetics.First-pass effect.Plasma protein binding.Volume of distribution.Zero-order kinetics.
Praziquantel
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 in Kucers’ The Use of Antibiotics, 2017
Severe hepatic insufficiency (Child class C) is associated with a doubling of the absorption half-life of praziquantel—potentially attributable to intestinal mucosal edema. The elimination half-life and increases in both maximum concentration in plasma (Cmax) and total drug exposure are attributable to a reduction in drug metabolism. However, these do not appear to correlate with an increased risk of significant drug toxicity (see below under 5b, Drug distribution) (Mandour et al., 1990; Watt et al., 1991; el Guiniady et al., 1994). Standard doses can therefore be administered to patients with severe hepatic dysfunction. It remains to be demonstrated if dose reductions are curative in this context.
Dose-dependent pharmacokinetics of midazolam in rats: influence of hepatic first-pass metabolism
Published in Xenobiotica, 2023
Run Li, Qingqing Wang, Zihou Liu, Like Xie, Zhipeng Diao, Ying Peng, Guangji Wang, Jianguo Sun
It is interesting that the half-life values in low doses prolonged compared to high dose after hepatic portal vein administration (Figure 3). And we performed a compartment model analysis on the data and we found that the elimination rates of the central chamber at 1 and 2 mg/kg were slower than that at 0.2 and 0.5 mg/kg (Table S1). This means that the elimination half-life in high dose was longer than in low doses. We envision a possibility for this observation is that the half-life of central chamber rather than the terminal half-life could be designated as the elimination half-life in this case. The terminal half-life is frequently referred to as the elimination half-life, as is often the case in pharmacokinetics. However, Riegelman et al. pointed out that the rate constant in the terminal phase could not be taken as the elimination rate constant (Riegelman et al. 1968), as is the same in Flip-flop pharmacokinetics.
A Review of New Medications and Future Directions of Medical Therapies in Glaucoma
Published in Seminars in Ophthalmology, 2020
Netarsudil is metabolized by corneal esterase to its main active metabolite, netarsudil-M1. Most of the medication stays local to the site of application, as little to no quantifiable amount of the medication was found systemically in a study by Levy et al.7 The elimination half-life of netarsudil from the cornea, conjunctiva, and vitreous humor ranged from 12 to 27 hours. While the elimination half-life from the retina-choroid-plexus, lens, and iris/ciliary body was longer, ranging from 68 to 112 hours.6 Clinically, this helps dictate dosing frequency, which is once daily for netarsudil 0.02%. Additionally, the elimination half-life is important in the time to reach steady state concentration as well as time to drug elimination, which are vital in monitoring medication effectiveness. In this case, it can take potentially up to 18 days or 4–5 times the half-life.
Effect of diammonium glycyrrhizinate on pharmacokinetics of omeprazole by regulating cytochrome P450 enzymes and plasma protein binding rate
Published in Xenobiotica, 2019
Lu Han, Rong Wang, Bin Wu, Yanqiu Gu, Yongfang Yuan
DAS version 3.0 (BioGuider Co., Shanghai, China) was used to analyze the plasma pharmacokinetic data and calculate the parameters. The maximum plasma concentration (Cmax) and the time taken for the drug to reach Cmax (Tmax) were obtained directly from the concentration–time curves. The linear regression of plasma concentration and time was calculated by the linear regression method, and the elimination rate constant (k) was calculated. The elimination half-life (t1/2) was calculated from the formula t1/2 = 0.693/k. The linear trapezoidal rule (AUC0–t) was used to calculate the area under the concentration–time curve. The mean residence time (MRT) was calculated with AUMC0–∞/AUC0–∞, whereby AUMC0–∞ represented the area under concentration–time curve since the initiation of the experiment. All data were presented as mean ± SD.
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