ABSTRACT
Coenzyme Q10 (CoQ(10)), a potential neuroprotective compound, was previously investigated at a dosage of 600 mg/day in Huntington's disease (HD) patients and demonstrated a trend toward slowing disease progression. Higher CoQ(10) dosages may prove beneficial. We investigated the tolerability and blood levels associated with 1,200, 2,400, and 3,600 mg/day of CoQ(10) in HD and healthy subjects. Twenty-eight subjects (20 HD, 8 healthy) enrolled in a 20-week open-label trial. Subjects started on 1,200 mg/day of CoQ(10), increasing every 4 weeks by 1,200 mg to a maximum dosage of 3,600 mg/day. Monthly evaluations included review of adverse events and CoQ(10) blood levels. Twenty-three subjects (82%) achieved the target dosage of 3,600 mg/day. Six subjects (2 healthy, 4 HD) withdrew prematurely (gastrointestinal (GI) symptoms in 3, worsening HD in 2, and 1 because of a fall). All three serious adverse events occurred in a single subject, and were deemed unrelated to CoQ(10). The most common adverse events seen were GI symptoms. Mean (± SD) CoQ10 blood levels achieved over the course of the trial were as follows: 1.26 ± 1.27 µg/mL (baseline, n = 28), 5.59 ± 2.24 µg/mL (1,200 mg/day, week 4, n = 26), 6.38 ± 3.25 µg/mL (2,400 mg/day, week 8, n = 25), 7.49 ± 4.09 µg/mL (3,600 mg/day, week 12, n = 23), and 6.78 ± 3.36 µg/mL (3,600 mg/day, week 20, n = 20). CoQ(10) was well tolerated with over 80% of subjects achieving the target dosage. Dosages of 2,400 mg/day may provide the best balance between tolerability and blood level achieved. Further studies examining the efficacy of 2,400 mg/day are planned.
Subject(s)
Huntington Disease/drug therapy , Ubiquinone/analogs & derivatives , Analysis of Variance , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Male , Treatment Outcome , Ubiquinone/administration & dosage , Ubiquinone/adverse effects , Ubiquinone/therapeutic useABSTRACT
Since the introduction of levodopa therapy in the 60's, there has yet to be a more efficacious drug identified for the symptomatic treatment of Parkinson's disease (PD). Perhaps more importantly, there has been little to no success finding agents that have proven effective in protecting against neurodegeneration. In fact, recent development efforts have been primarily directed at stabilizing the side effects (wearing off, drug-induced dyskinesias, motor fluctuations) that accompany prolonged levodopa therapy, such as catechol O-methyltransferase inhibiton to combat the side effects of levodopa therapy. This review also examines alternative strategies to levodopa therapy, including potential adjuncts therapies, recent patents and future directions to be evaluated for neuroprotection. While dopamine agonists are inferior to levodopa in controlling motor symptoms, potential benefits and drawbacks with this class of drugs are presented. Potential neuroprotective agents such as monoamine oxidase-B inhibitors are also examined for their therapeutic benefit as well as their potential to slow disease progression. Neuroprotection will continue to be an important area of research in CNS drug development.
Subject(s)
Antiparkinson Agents/therapeutic use , Neuroprotective Agents/therapeutic use , Parkinson Disease/drug therapy , Animals , Dopamine Agonists/therapeutic use , Drug Administration Routes , Humans , Levodopa/therapeutic use , Monoamine Oxidase Inhibitors/therapeutic useSubject(s)
Ubiquinone/analogs & derivatives , Administration, Oral , Adult , Area Under Curve , Back Pain/chemically induced , Biological Availability , Capsules , Coenzymes/administration & dosage , Coenzymes/pharmacokinetics , Cross-Over Studies , Double-Blind Method , Female , Gelatin/chemistry , Headache/chemically induced , Humans , Male , Pruritus/chemically induced , Sex Factors , Sinusitis/chemically induced , Time Factors , Ubiquinone/administration & dosage , Ubiquinone/pharmacokinetics , Vitamins/administration & dosage , Vitamins/adverse effects , Vitamins/pharmacokineticsABSTRACT
Sialorrhea is a relatively common symptom in idiopathic Parkinson's disease and related conditions for which most of the accepted treatments are either highly invasive or may cause substantial systemic side effects. This study describes an open-label pilot study of sublingual atropine drops for the treatment of sialorrhea in 7 patients (6 with Parkinson's disease, 1 with progressive supranuclear palsy). Participants demonstrated statistically significant declines in saliva production, both objectively and subjectively. Self-reported drooling severity showed a significant decline between baseline and 180 minutes, t(6) = 3.240 P < 0.025 (eta(2) = 0.636), and between baseline and 1 week, t(6) = 4.583 P < 0.005 (eta(2) = 0.778). Objectively measured saliva production decreased significantly between baseline and the 1-week follow-up, t(6) = 2.711 P < 0.05 (eta(2) = 0.551). Delirium occurred in 1 patient (concurrent with a urinary tract infection), and 2 patients experienced worsening of hallucinations (active hallucinosis was concealed by both individuals to allow participation in the trial). The remaining trial participants did not experience any anticholinergic side effects. This trial shows that, in selected patient populations, sublingual atropine is a simple and inexpensive treatment for sialorrhea associated with parkinsonism.