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... With regards to safety profile, 89% of the patients treated with CSAI report at least one side effect [74]. It is estimated that 1 in 10 patients decide to discontinue the medication due to side effects [75]. The most common adverse reaction is subcutaneous nodules (50%) [42,76]. ...
Significant advances in the symptomatic treatment of Parkinson disease (PD) have occurred since the discovery of levodopa (LD). Perhaps as a testament to its unparalleled efficacy, novel formulations aiming to optimize LD delivery to obtain better bioavailability, longer duration of effect and less plasma level fluctuations remain a major focus of drug development, nearly 5 decades since it was first commercially used. In addition, alternative apomorphine delivery formulations are also in development to provide rapid-acting, needle-free agents for the management of “off” episodes in patients experiencing motor fluctuations. “Non-dopaminergic” approaches have also emerged as promising treatments targeting different pathways to enhance the modulation of dopaminergic and neuroprotective mechanisms. This paper focuses on reviewing the evidence on the latest advances in non-surgical, symptomatic motor PD treatment.
... Conversely, apomorphine appears to be hardly metabolized at all by microsomal cytochrome P450 systems (CYPs) [49] In vitro, high concentrations of apomorphine inhibit human CYP1A2, 2D6 and 3A4 [57,62] (K i = 7.4, 27 and 18 lm, respectively [57]). However, apomorphine may not possess any significant inhibitory capabilities against human CYPs in vivo, considering the C max values obtained after its administration [57,63]. Apomorphine is therefore unlikely to significantly inhibit the CYP-mediated metabolism of other drugs, explaining the small number of drug interactions reported with this compound [57]. ...
... Allergic contact dermatitis in carers or health professionals who prepare and administer aqueous solutions of apomorphine hydrochloride have been reported [252][253][254]. Tolerance induction protocols or desensitization procedures, featuring increasing concentrations of apomorphine and pretreatment with cetirizine, may help to alleviate hypersensitivity in individuals where no alternative treatments are available [63]. ...
The present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson’s disease (PD). The chemistry, structure–activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic. Its pharmacokinetics and pharmacodynamics are complex and subject to interindividual variability, particularly for subcutaneous absorption and metabolism. Subcutaneous apomorphine, either as injections or infusion, is particularly useful for the treatment of PD motor symptoms and growing evidence supports its clinical value for nonmotor disorders. Owing to interindividual variability and sensitivity, apomorphine treatment must be tailored to each patient. While the subcutaneous route has been the gold standard for decades, the search for alternative routes is ongoing, with promising results from studies of pulmonary, sublingual and transdermal routes. In addition, the potential of apomorphine as a disease-modifying therapy deserves to be investigated, as well as its ability to induce brain plasticity through chronic infusion. Moreover, the ongoing progress in the development of analytical methods should be accompanied by new pharmacokinetic and pharmacodynamic studies of apomorphine metabolism and sites of action in humans, as its biochemistry has yet to be fully described.
