A loading dose given intravenously has been found to achieve steady-state levels more rapidly with oral vortioxetine therapy. The pharmacokinetics of vortioxetine are known to be linear and dose proportional over a range of 2.5 to 75 mg for single doses and 2.5 to 60 mg for multiple doses. Food has no influence on the pharmacokinetics of vortioxetine.The apparent volume of distribution of vortioxetine is large and ranges from 2,500 to 3,400 L after single or multiple doses of 5 to 20 mg vortioxetine, with extensive extravascular distribution. The plasma protein binding of vortioxetine is approximately 98 or 99%, with about 1.25 ± 0.48% free or unbound.Vortioxetine is extensively metabolized by oxidation via cytochrome P450 enzymes and subsequent glucuronidation via UDP-glucuronosyltransferase. CYP2D6 is the primary enzyme involved in the metabolism of vortioxetine, but others including CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4/5 are also involved. It is also metabolized by alcohol dehydrogenase, aldehyde dehydrogenase, and aldehyde oxidase. Six metabolites of vortioxetine have been identified. The major metabolite of vortioxetine (Lu AA34443) is inactive and its minor active metabolite (Lu AA39835) is not thought to cross the blood–brain barrier. The remaining metabolites are glucuronide conjugates. Hence, vortioxetine itself is thought to be primarily responsible for its pharmacological activity.The estimated total clearance of vortioxetine ranges from 30 to 41 L/h. The elimination half-life of vortioxetine is 66 hours, with a range of 59 to 69 hours after single or multiple doses. Elimination of vortioxetine is almost entirely via the liver (99%) rather than the kidneys (<1%).
Testicular pain, also known as scrotal pain, occurs when part or all of either one or both testicles hurt. Pain in the scrotum is also often included. Testicular pain may be of sudden onset or of long duration.Causes range from non serious muscular skeletal problems to emergency conditions such as Fournier gangrene and testicular torsion. The diagnostic approach involves making sure no serious conditions are present. Diagnosis may be supported by ultrasound, urine tests, and blood tests.Pain management is typically given with definitive management depending on the underlying cause. Definition
Testicular pain is when part or all of either one or both testicles hurt. Pain of the scrotum is often included. It may be either acute, subacute or chronic depending on its duration. Chronic scrotal pain
Chronic scrotal pain (pain for greater than 3 months) may occur due to a number of underlying conditions. It occurs in 15-19% of men post vasectomy, due to infections such as epididymitis, prostatitis, and orchitis, as well as varicocele, hydrocele, spermatocele, polyarteritis nodosa, testicular torsion, previous surgery and trauma. In 25% of cases the cause is never determined. The pain can persist for a long and indefinite period of time following the vasectomy, in which case it is termed post-vasectomy pain syndrome (PVPS). Differential diagnosis
The differential diagnosis of testicular pain is broad and involves conditions from benign to life-threatening. The most common causes of pain in children presenting to the emergency room are testicular torsion (16%), torsion of a testicular appendage (46%), and epididymitis (35%).