Ebastine is an antihistamine which blocks H1-receptors through its carboxylic acid metabolite. Ebastine is indicated for the treatment of allergic rhinitis and chronic idiopathic urticaria.

Warfarin, (S)- is an oral anticoagulant, S-enantiomer of warfarin, that having a greater pharmacologic potency than the R-enantiomer. Clinically available warfarin is a racemic mixture of (R)- and (S)-warfarin, and the (S)-enantiomer has 3 to 5 times greater anticoagulation potency than its optical congener. Both enantiomers are eliminated extensively via hepatic metabolism with low clearance relative to hepatic blood flow. The scientific debate on the contribution of the R- Warfarin -to-S- Warfarin effect is a long and conflictual story. It has shown that the pharmacodynamic response to (R/S)-Warfarin 25 mg (a mixture of equal amounts of S-Warfarin and R- Warfarin) was nearly twice that of S-Warfarin 12.5 mg given alone, thus indicating the substantial contribution of R-Warfarin to the (R/S)-Warfarin effect. (R/S)-Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, and pulmonary embolism. It is also indicated for the prophylaxis and/or treatment of the thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of the vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K1 epoxide.

Nicotinyl methylamide (N-methylnicotinamide) is an experimental drug with no approved indication or marketed formulation. Nicotinyl methylamide is a metabolite of niacin (or nicotinamide) and is commonly found in human urine. However low levels of urinary excretion of N-methylnicotinamide indicates niacin deficiency. In patients with liver cirrhosis nicotinamide methylation is increased leading to a rise in urinary N-methylnicotinamide. The hyperfunction of this methylating pathway might play a protective role against the toxic effect of intracellular accumulation of nicotinamide deriving from the catabolic state of cirrhosis. N-methylnicotinamide is known to inhibit choline transport and reduce choline clearance out of the brain. N-methylnicotinamide has been found to be a microbial metabolite. N-methylnicotinamide inhibits arterial thrombosis in hypertensive rats. N-methylnicotinamide via production/release of prostacyclin inhibits arterial thrombosis development. The antithrombotic effect of N-methylnicotinamide is accompanied by platelet inhibition and enhanced fibrinolysis, due to the decrease production of plasminogen activator inhibitor -1.

Otilonium is a musculotropic spasmolytic agent belonging to the family of quaternary ammonium derivatives and successfully used in the treatment of patients affected by Irritable bowel syndrome (IBS) due to its specific pharmacokinetic and pharmacodynamic properties. The positive polarity of the head of the Otilonium molecule determines the main pharmacokinetic property of this drug: a minimal systemic absorption and the consequently high safety profile. Studies on animal models revealed a specific Otilonium accumulation in colonic circular muscle at therapeutic µm concentrations, while its plasma levels were 1000 times lower, together with a poor penetration of the drug in the central nervous system. Consistently, after oral administration to healthy volunteers, the Otilonium plasmatic concentration was very low, less than 1% of the drug was eliminated by urine, and 97% was eliminated by feces. Recent clinical studies showed comparable safety and tolerability for Otilonium and placebo. Otilonium was shown to inhibit the main patterns of human sigmoid motility in vitro, including: the tone of smooth muscle cells (SMCs); the rhythmic phasic contractions induced by the interstitial cells of Cajal; and the strong contractions induced by stimulation of enteric motor neurons mainly by blocking the calcium influx through L-type calcium channels on SMCs. Recent in vitro studies using cultured human colonic SMCs to further assess the musculotropic spasmolytic properties of Otilonium confirmed that this drug causes smooth muscle relaxation through the inhibition of voltage-gated calcium channels (L-type > T-type) and the inhibition of muscarinic and tachykinergic effects.

Entacapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT), that in combination with carbidopa and levodopa used for the treatment of Parkinson's disease. Physiological substrates of COMT include DOPA, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. When decarboxylation of levodopa is prevented by carbidopa, COMT becomes the major metabolizing enzyme for levodopa, catalyzing its metabolism to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD). When entacapone is given in conjunction with levodopa and carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and carbidopa alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson’s disease. The higher levodopa levels may also lead to increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. When 200 mg entacapone is coadministered with levodopa/carbidopa, it increases levodopa plasma exposure (AUC) by 35-40% and prolongs its elimination half-life in Parkinson’s disease patients from 1.3 to 2.4 hours. Plasma levels of the major COMT-mediated dopamine metabolite, 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD), are also markedly decreased proportionally with increasing dose of entacapone. In animals, while entacapone enters the CNS to a minimal extent, it has been shown to inhibit central COMT activity. In humans, entacapone inhibits the COMT enzyme in peripheral tissues. The effects of entacapone on central COMT activity in humans have not been studied.

Cupric salicylate is an anti-inflammatory agent which was used as pain relief for patients with osteoarthritis, rheumatoid and other degenerative diseases (as a copper-salicylate complex). The preparation seem to be discontinued for now.

Zyrconium cyclosilicate (ZS-9) is a selective oral sorbent that traps potassium ions throughout the gastrointestinal tract. ZS-9 is not systemically absorbed; accordingly, the risk of systemic toxicity may be minimized. ZS-9 was originally developed by ZS Pharma, and later licensed to AstraZeneca. In 2018 the FDA has approved ZS-9 for treatment of hyperkalemia.

Tebipenem pivoxil is an oral carbapenem prodrug that was originated by Wyeth (now Pfizer). It was approved by Pharmaceuticals and Medical Devices Agency of Japan (PMDA) on Apr 22, 2009. It was developed and marketed as Orapenem® by Meiji Seika in Japan. Tebipenem pivoxil is a broad-spectrum orally-administered antibiotic, from the carbapenem subgroup of β-lactam antibiotics. Carbapenems are a class of beta-lactam antibiotics, which act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. It is used to treat otorhinolaryngological infection, otitis media and bacterial pneumonia. Orapenem® is available as granules for oral use, containing 100 mg Tebipenem pivoxil/g granules. According to the weight of children, 4 mg/kg, and twice a day after dinner.

Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. In addition it inhibits prostaglandin biosynthesis. Well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding.

Asunaprevir is a direct acting antiviral agent (DAA) against the hepatitis C virus Asunaprevir is an inhibitor of the HCV NS3/4A serine protease complex. This NS3/4A enzyme complex is responsible for processing the HCV polyprotein to yield mature viral proteins required for viral replication. The combination of daclatasvir + asunaprevir [Daklinza(®) + Sunvepra(®)], two direct-acting antiviral agents, has been developed by Bristol-Myers Squibb for the treatment of patients with chronic hepatitis C virus (HCV) genotype 1 infections, including those with compensated cirrhosis.