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Essential Pharmacology of Abused Drugs
Published in Frank Lynn Iber, Alcohol and Drug Abuse as Encountered in Office Practice, 2020
Ethyl alcohol is fully soluble in water, and its volume of distribution is relatively low. Ether is highly lipid-soluble and has a very high volume of distribution because it dissolves in lipid stores. Some amphetamines are tightly bound to albumin in the plasma and have a volume of distribution that is about the same as the albumin space. Drugs with a high volume of distribution take longer to be removed from the body than those with a low volume. Excretion, liver biotransformation, and renal excretion can take place only on that portion of drug in the circulation. Drug in other sites must diffuse into the circulation before these modes of removal can occur. When biotransformation occurs, the lipid solubility is diminished and the water solubility is increased, a fact which nearly always decreases the volume of distribution and accelerates the removal of the biotransformed product.
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
Quite often, the half-life of a drug is used as an indicator for systemic exposure. Half-life is a secondary pharmacokinetic property, as it is determined by clearance and volume of distribution (t1/2 = 0.693 · Vd/CL). While clearance describes the ability of the body to eliminate the drug, volume of distribution (Vd) is the pharmacokinetic parameter that provides information on the extent of drug distribution into tissue compartments.
The Study of Drug Metabolism Using Radiotracers
Published in Graham Lappin, Simon Temple, Radiotracers in Drug Development, 2006
The volume of distribution is thus defined as the amount of drug in the body divided by the plasma drug concentration. For an intravenous dose, the amount in the body is the amount injected. The concentration of a drug in systemic circulation is heavily dependent upon how the drug is distributed in the body. If the drug is sequestered in a deep body compartment (e.g., fat), then the plasma concentration will diminish and the volume of distribution will rise. If the volume of distribution for a given drug is known, then the plasma concentration can be predicted from a given intravenous dose.
Effect of quercetin on the pharmacokinetics of selexipag and its active metabolite in beagles
Published in Pharmaceutical Biology, 2022
Shun-bin Luo, Er-min Gu, Yu-ao Chen, Shi-chen Zhou, Chen Fan, Ren-ai Xu
The pharmacokinetic parameters of selexipag and ACT-333679 after orally administered selexipag with and without quercetin pre-treatment in beagles were calculated by the DAS 2.0 software (Shanghai University of Traditional Chinese Medicine, China) in non-compartmental analysis. Cmax was the maximum observed plasma concentration, Tmax was the time to reach the maximum observed plasma concentration. AUC0–t and AUC0–∞ were the area under the concentration-time curve to the last time point and area to infinity, respectively. The apparent volume of distribution (Vd) refers to the ratio of the drug dose to blood concentration after a drug has reached dynamic equilibrium in the body. Plasma clearance (CL) is the total clearance rate of drugs in the liver and kidney, that is, how much volume of plasma is cleared of drugs per unit time.
An evaluation of mitapivat for the treatment of hemolytic anemia in adults with pyruvate kinase deficiency
Published in Expert Review of Hematology, 2022
Andrew B. Song, Hanny Al‐Samkari
In the phase 1 studies, mitapivat was readily absorbed in both the fasting and fed state. With doses of mitapivat of 700 mg or more, dose-normalized Cmax decreased with increasing doses. In the MAD study, dose-normalized Cmax and AUC0-τ on day 14 increased proportionally for the 15- and 60-mg dose cohorts but decreased with increasing dose from 120- to 700-mg dose cohorts. Pharmacokinetic parameters suggested autoinduction of mitapivat metabolism at doses of 120 mg every 12 hours or greater with plasma trough levels decreasing with subsequent doses and dose normalized Cmax decreasing with increasing doses of 120 mg or greater. Steady state mean plasma trough level was achieved on day 2 in the 15-mg dose cohorts and on day 7 in the 60-mg dose cohort. The terminal half-life was estimated to be 3–6 hours. 98% of mitapivat is protein bound in plasma. The volume of distribution is 42.5 L. Additional pharmacokinetic parameters are summarized in Table 1.
IL-23 inhibition for the treatment of psoriatic arthritis
Published in Expert Opinion on Biological Therapy, 2022
Raagav Mohanakrishnan, Secia Beier, Atul Deodhar
Studies indicate the mean steady-state trough serum concentration was approximately 1.2mcg/ml, following 100 mg guselkumab injection at week 0, 4, and every 8 weeks [35]. The median time to reach peak plasma concentration after a single 100 mg subcutaneous injection was around 5.5 days and the approximate bioavailability was 49% [35]. Currently, the bioavailability of guselkumab in synovial fluid or psoriatic skin is not available. The volume of distribution was 13.5 L in subjects studied with plaque psoriasis [35]. The mean systemic clearance was 0.516 L/day and the mean half-life was 15 to 18 days in subjects with plaque psoriasis [35]. Clearance and volume of distribution increases as body weight increases. The precise pathway by which guselkumab is metabolized has not been established [35].