IACS-8968 S-enantiomer

Escitalopram

Escitalopram is a medication used to manage and treat major depressive and generalized anxiety disorders. It is the S-enantiomer of citalopram and is the most selective of SSRIs. It is in the selective serotonin reuptake inhibitor class of drugs. Escitalopram is also used off-label for social anxiety disorder, obsessive-compulsive disorder, panic disorder, posttraumatic stress disorder, premenstrual dysphoric disorder, and vasomotor symptoms of menopause. This activity will highlight the mechanism of action, adverse event profile, and other key factors (e.g., dosing, pharmacodynamics, pharmacokinetics, monitoring, relevant interactions, adverse events) pertinent to members of the healthcare team in the management of patients with depression, anxiety, and other related conditions.

Escitalopram

Escitalopram, a selective serotonin reuptake inhibitor (SSRI) was recently approved by the United States Food and Drug Administration (FDA) for the treatment of major depression. This chapter reviews preclinical and clinical studies with escitalopram, focusing on its therapeutic profile of action and tolerability. Escitalopram is the S-enantiomer of the racemic SSRI citalopram. It has been proposed that the S-enantiomer of citalopram is the isomer that holds antidepressant efficacy, and that the R-enantiomer is clinically inactive; preclinical and clinical data support this. Based on in vitro radioligand binding data, escitalopram is the most selective SSRI available. Hypotheses that escitalopram has a more rapid onset of action or fewer adverse effects than citalopram have not yet been fully documented in published studies, although its profile is at least comparable to citalopram. Escitalopram is more effective than placebo in the treatment of major depression and as effective as other SSRIs, including citalopram. Comparable to other SSRIs, it is well tolerated, safe in overdose and has a low incidence of adverse effects or drug interactions.

Clinical pharmacokinetics of ibuprofen. The first 30 years

Ibuprofen is a chiral nonsteroidal anti-inflammatory drug (NSAID) of the 2 arylpropionic acid (2-APA) class. A common structural feature of 2-APANSAIDs is a sp3-hybridised tetrahedral chiral carbon atom within the propionic acid side chain moiety with the S-(+)-enantiomer possessing most of the beneficial anti-inflammatory activity. Ibuprofen demonstrates marked stereoselectivity in its pharmacokinetics. Substantial unidirectional inversion of the R-(-) to the S-(+) enantiomer occurs and thus, data generated using nonstereospecific assays may not be extrapolated to explain the disposition of the individual enantiomers. The absorption of ibuprofen is rapid and complete when given orally. The area under the plasma concentration-time curve (AUC) of ibuprofen is dose-dependent. Ibuprofen binds extensively, in a concentration-dependent manner, to plasma albumin. At doses greater than 600mg there is an increase in the unbound fraction of the drug, leading to an increased clearance of ibuprofen and a reduced AUC of the total drug. Substantial concentrations of ibuprofen are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Ibuprofen is eliminated following biotransformation to glucuronide conjugate metabolites that are excreted in urine, with little of the drug being eliminated unchanged. The excretion of conjugates may be tied to renal function and the accumulation of conjugates occurs in end-stage renal disease. Hepatic disease and cystic fibrosis can alter the disposition kinetics of ibuprofen. Ibuprofen is not excreted in substantial concentrations into breast milk. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), cholestyramine and methotrexate. A relationship between ibuprofen plasma concentrations and analgesic and antipyretic effects has been elucidated.

Esomeprazole

Esomeprazole is the S-enantiomer of the proton-pump inhibitor, omeprazole. Limited information indicates that maternal doses of 10 mg daily produce low levels in milk and would not be expected to cause any adverse effects in breastfed infants.

Citalopram

Citalopram and escitalopram are selective serotonin reuptake inhibitors (SSRIs) and widely used antidepressants. Citalopram is a racemic mixture, whereas escitalopram is its S-enantiomer. Both agents have similar profiles of clinical efficacy and side effects. Both have been associated with rare instances of clinically apparent acute liver injury.