In an open-label, fixed-dose, 2-week trial in eight males with schizophrenia, PET scans of dorsal striatal regions (caudate nucleus and putamen) and ventral striatum (nucleus accumbens) showed maximum occupancy (‡ 90%) at a 3-mg target dose of cariprazine following 14 d of treatment [40,41]. After 14 d of cariprazine 1.5 mg/d, receptor occupancy was 69% in the caudate nucleus, 69% in the nucleus accumbens, and 75% in the putamen". Pharmacokinetics
Cariprazine has high oral bioavailability and can cross the blood brain barrier easily in humans because it is lipophilic. In rats, the oral bioavailability was 52% (with a dose of 1 mg/kg).Cariprazine is metabolized primarily by the cytochrome P450 3A4 isoenzyme (CYP3A4), with some minor metabolism by CYP2D6. Cariprazine does not induce the production of CYP3A4 or CYP1A2 in the liver, and weakly, competitively inhibits CYP2D6 and CYP3A4. Research
Cariprazine is also potentially useful as an add-on therapy in major depressive disorder. It is being developed jointly by AbbVie and Gedeon Richter Plc, with AbbVie responsible for commercialization in the U.S., Canada, Japan, Taiwan and certain Latin American countries (including Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Mexico, Peru and Venezuela). In February 2022 AbbVie requested FDA approval for adjunctive treatment for major depressive disorder. References
External links
"Cariprazine". Drug Information Portal. U.S. National Library of Medicine.
Aldurazyme is administered as a slow intravenous infusion. The recombinant enzyme is 628 amino acids in length with 6 N-linked oligosaccharide modification sites and two oligosaccharide chains terminating in mannose sugars. Medical use
Aldurazyme is indicated in the US for people with Hurler and Hurler-Scheie forms of Mucopolysaccharidosis I (MPS I) and for people with the Scheie form who have moderate to severe symptoms.Aldurazyme is indicated in the EU for long-term enzyme replacement therapy in patients with a confirmed diagnosis of mucopolysaccharidosis I (MPS I; alpha-L-iduronidase deficiency) to treat the nonneurological manifestations of the disease.Aldurazyme was approved for medical use in the United States and in the European Union in 2003. Pre-clinical work
Dosing for human clinical studies was based on canine MPS I studies. Clinical trials
Three clinical trials were performed to establish the pharmacology, efficacy, and safety of weekly intravenous administration of the drug. These studies included a Phase I open-label study, a Phase III randomized, double-blind, placebo-controlled study, and a Phase III open-label extension study. A Phase II Young Pediatric study was also conducted.Clinical trials and post-market safety data indicate that the most common adverse side effect of Aldurazyme is allergic reaction. In order to prevent allergic reaction and respiratory distress, the packet insert of Aldurazyme suggests that patients be administered antihistamines before infusion. Allergic reaction occurs in approximately 1% of patients. It is recommended that patients who are high-risk for respiratory distress be given their infusion in a facility equipped to deal with an anaphylactic response.