China
Africa
Explore chapters and articles related to this topic
Sedative and Hypnotic Drugs
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Arup Kumar Misra, Pramod Kumar Sharma
Meprobamate is well absorbed and undergoes metabolization in the liver by hydroxylation and glucuronidation. The elimination half-life of the drug is directly proportional to the amount of drug administered. There is increase in plasma half-life of meprobamate due to the cumulative effects of the drug given for a prolong duration. The adverse drug effects are drowsiness, ataxia, impair learning, motor incoordination, and prolong reaction time. Its abrupt discontinuation leads to withdrawal syndrome in the form of anxiety, insomnia, tremors, hallucinations, etc. (Ramchandani et al., 2006).
Noncompartmental and System Analysis
Published in John G. Wagner, Pharmacokinetics for the Pharmaceutical Scientist, 2018
The elimination half-life, t½, is given by Equation (168), where λi is the smallestexponent(i.e.,λ1 Ą λ2 Ą λn) and is the apparent elimination rate constant corresponding to the very tail end of the concentration-time curve.
M
Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Mean AUC0-∞ increased by 4%, 60%, and 115% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects. The terminal elimination half-life increased by 18%, 41%, and 95% in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy subjects.
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.
Opioid MOP receptor agonists in late-stage development for the treatment of postoperative pain
Published in Expert Opinion on Pharmacotherapy, 2022
Qiu Qiu, Joshua CJ Chew, Michael G Irwin
M6G has four-times less affinity for the MOP receptor [74]. Both the volume of distribution and clearance of M6G is lower than morphine. M6G is less lipophilic resulting in a slower distribution into the central nervous system and this confers a slower onset compared with morphine [75,77–79]. After oral administration of M6G, two peak concentrations are observed (3.5 hours and 21.3 hours after 50 mg). A potential mechanism is that M6G was hydrolyzed into morphine within the colon, and this morphine was subsequently reabsorbed and metabolized back into M6G, producing a second peak [80]. Clinically effective doses of M6G were shown to be greater than 0.15 mg/kg. Doses of less than 5 mg, used in early trials, showed no analgesic effect over placebo. The duration of action of M6G was 12–24 hours, as compared to 2–4 hours for morphine [77,81]. Unlike morphine, M6G is almost exclusively eliminated through the kidneys with minimal enterohepatic circulation. Thus, the elimination half-life is significantly increased in patients with renal impairment, potentially to more than 24 hours [82,83].
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.