2010; Downham et al. 1978]. OLAI is a salt-based depot combining olanzapine and pamoic acid, the properties of which make the compound practically insoluble in aqueous solution but with substantially greater solubility and dissolution rates in plasma than in environments similar to muscle tissue [McDonnell et al. 2010]. The clinical CDK inhibitor implications are that solubility and dissolution become far more rapid should the compound be inadvertently

injected intravascularly [McDonnell et al. 2010]. These pharmacokinetic and pharmacodynamic properties suggest inadvertent vascular injection is the most likely explanation for the temporal and clinical symptoms of PDSS [McDonnell et al. 2010; Detke et Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical al. 2010]. In a laboratory study of this issue no other explanation relating to product quality or administration could coherently explain PDSS [McDonnell et al. 2010]. No predictors of PDSS, such as dose administered, could be defined [McDonnell et al. 2010; Detke et al. 2010]. Supportive of this hypothesis are the plasma olanzapine levels measured during the PDSS event in 12 of the 30 initial cases reported, with levels being higher than the expected range of

5–73 ng/ml [McDonnell et al. 2010]. Concentrations Inhibitors,research,lifescience,medical exceeded 100 ng/ml in all cases and measured more than 600 ng/ml in some cases, but returned to the expected range within 72 h [McDonnell et al. 2010]. The expected therapeutic range was derived from clinical studies of OLAI in which the range 5–73 ng/ml equated to the 10th percentile for 150 mg/2 weeks and the 90th percentile for 300 mg/2 weeks at steady state [Kane et al. 2010]. Intravascular injection with long-acting risperidone Inhibitors,research,lifescience,medical has been reported with different symptomatology due to the microsphere formulation leading to retinal artery occlusion in a patient with patent foramen ovale [Tang and Weiter, 2007]. However, the clinical symptoms and signs of PDSS have not been observed Inhibitors,research,lifescience,medical with risperidone long-acting injection or paliperidone palmitate [Alphs et al.

2011]. In 15 completed trials, using approximately 115,000 injections with risperidone long-acting injection, there were no cases of PDSS and only a single case in the placebo cohort in 10 completed trials, using 33,906 injections in paliperidone palmitate studies [Alphs et al. 2011]. The clinical issue often relates to the practicality Astemizole of providing 3 h of observation for each patient, which can be undertaken by any appropriately qualified healthcare professional, and accompaniment home, which does not need to be done by a healthcare professional. Currently OLAI is the only depot antipsychotic for which such observation is mandated, and to achieve it, incorporating patients into an existing unit may be an option. In this case an existing daycare unit staffed by healthcare professionals has proven a reasonable option that has also allowed patients to take advantage of ongoing psycho-educational programmes.