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Pharmacokinetic determinants of clinical activity
Published in Adam Doble, Ian L Martin, David Nutt, Calming the Brain: Benzodiazepines and related drugs from laboratory to clinic, 2020
Adam Doble, Ian L Martin, David Nutt
Certain benzodiazepines are extensively metabolised during their first transit from the intestine through the liver to the general circulation. The maximal plasma concentrations of these drugs are thus likely toincreasewhen metabolic function decreases with age. Drugs with such a first-pass effect include triazolam, temazepam and lorazepam. The consequence of this is that elderly patients will be exposed to higher circulating plasma levels than younger patients.
Adrenergic Antagonists
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
It is an adrenergic β1 selective receptor antagonist without having ISA and MSA (Brunton et al., 2011; Florey, 2008). It is employed in the treatment of essential hypertension, tachycardia, heart failure, angina pectoris, vasovagal syncope, secondarily in the prevention of myocardial infarction, migraine treatment, and hyperthyroidism. It can be administered orally and used intravenously as metoprolol tartrate. It is helpful in chronic heart failure. After an oral dose, the drug has 40% bioavail-ability because of first-pass effect. Extensive metabolism occurs in the liver by the enzyme CYP2D6. The drug excretion takes place via the urine after biotransformation and 85% drug excreted are metabolites. The drug has a half-life of about 4 h (Brunton et al., 2011; Florey, 2008).
Toxicology
Published in Aruna Bakhru, Nutrition and Integrative Medicine, 2018
Drugs administered orally are absorbed from the gastrointestinal tract, carried via the hepatic portal vein to the liver, and then undergo some metabolism by the liver before the drug has even had the opportunity to work. This removal of a drug by the liver, before the drug has become available for use, is called the first-pass effect. Some drugs, when swallowed and absorbed, will be almost totally inactivated by the first-pass effect (e.g., nitroglycerin). The first-pass effect can, however, be avoided if the drug is given by another route. Thus, nitroglycerin when administered sublingually or transdermally, avoids first-pass metabolism by the liver and is able to cause a therapeutic effect.
Formulation, development, and in-vitro/ex-vivo evaluation of vaginal bioadhesive salbutamol sulfate tablets for preterm labor
Published in Pharmaceutical Development and Technology, 2020
Amal S. M. Abu El-Enin, Asmaa M. Elbakry, Rania El Hosary, Marwa Ahmed Fouad Lotfy
Africa showed minimal progress to overcome this problem. Egypt is ranked 144 amongst 162 countries with prematurity-related deaths comprising about 28.5% of all under-5 deaths in Egypt (Liu et al. 2012; Lawn et al. 2013). Tocolytic drugs function by prolonging pregnancy in case of preterm labor, allowing the fetus to be more mature in the uterus before being born (Roberts et al. 2017). β2 agonists as salbutamol sulfate and terbutaline sulfate have been used for the treatment of preterm labor in hospitals since 1980. They are given as intravenous infusion then treatment maintained via oral tablets. Parenteral and oral salbutamol may cause some side effects, such as tachycardia, anxiety, and chill. It has also a short half-life 4–6 h (Zulfiqar and Iftikhar 2016). It suffers from first-pass effect in the liver and gut wall. Salbutamol sulfate is a class I drug according to biopharmaceutical classification, it is a highly water-soluble drug with a pKa of 9.2 and a log p value of 0.11 (Prasanth et al. 2011).
Analytical tools and evaluation strategies for nanostructured lipid carrier-based topical delivery systems
Published in Expert Opinion on Drug Delivery, 2020
Sheefali Mahant, Rekha Rao, Eliana B. Souto, Sanju Nanda
Topical delivery of active pharmaceutical ingredients (APIs) for the treatment of cutaneous and musculoskeletal disorders is favorable due to a number of reasons [2]. Not only the systemic side effects are reduced but also the plasma API levels obtained after topical administration are relatively constant. This is particularly useful in case of APIs which undergo rapid elimination and need to be administered frequently. Moreover, first pass effect due to hepatic metabolism of drugs is ruled out. Pain-free administration and sustained release of drugs can also be achieved. Owing to these merits, transdermal application of APIs has also been extensively explored [3–5]. Topical API delivery to skin is, however, a challenge in terms of achieving optimum API concentration in different strata of the skin and controlling its release from the carrier system [2].
Genetic polymorphisms of human hepatic OATPs: functional consequences and effect on drug pharmacokinetics
Published in Xenobiotica, 2020
Yingmin Nie, Jingjie Yang, Shuai Liu, Ruiqi Sun, Huihui Chen, Nan Long, Rui Jiang, Chunshan Gui
Liver is an important organ for drug disposition in the human body. After oral administration, many clinically important drugs will undergo first-pass elimination whereby the concentrations of drugs might be greatly reduced before they reach the systemic circulation (Pond & Tozer, 1984). Liver is the major site at which first-pass effect takes place and hepatic drug transporters play an important role in this process. Organic anion transporting polypeptides (OATPs), encoded by SLCO genes, are members of an important family of transmembrane influx transporters which belong to solute carrier (SLC) superfamily (Hediger et al., 2004). OATPs mediate sodium- and ATP-independent transport of various endo- and exogenous substances (Hagenbuch & Meier, 2003, 2004). Human OATPs comprise 643–722 amino acid residues and consist of 12 transmembrane domains with 6 extracellular loops and 5 intracellular loops and N- and C-terminals located intracellularly (Hagenbuch & Gui, 2008).