Scopolamine pharmacokinetics

Ebert U, Oertel R, Kirch W. Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects. Int J Clin Pharmacol Ther 2000 38(11) 523-531. 

Ebert U, Siepmann M, Oertel R, Wesnes KA, Kirch W. (1998). Pharmacokinetics and pharmacodynamics of scopolamine after subcutaneous administration. J Clin Pharmacol. 38(8) 720-26. 

Mechanism of Action Competitive inhibitors of the muscarinic actions of acetylcholine, acting at receptors located in exocrine glands, smooth and cardiac muscle, and intramural neurons. Composed of 3 main constituents atropine, scopolamine, and hyoscyamine. Scopolamine exerts greater effects on the CNS, eye, and secretory glands than the constituents atropine and hyoscyamine. Atropine exerts more activity on the heart, intestine, and bronchial muscle and exhibits a more prolonged duration of action compared to scopolamine. Hyoscyamine exerts similar actions to atropine but has more potent central and peripheral nervous system effects. TherapeuticEffect Peripheral anticholinergic and antispasmodic action, mild sedation. Pharmacokinetics None known... 

Chuang DM, Gao X-M, Paul SM N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells. Mol Pharmacol 42 210-216, 1992 Chugh Y, Saha N, Sankaranarayanan A, et al Enhancement of memory retrieval and attenuation of scopolamine-induced amnesia following administration of S-HTj antagonist ICS 205-930. Pharmacol Toxicol 69 105-106, 1991 Ciraulo DA, Jaffe JH Tricyclic antidepressants in the treatment of depression associated with alcoholism. Clin Psychopharmacol 1 146, 1981 Ciraulo DA, Barnhill JG, Jaffe JH Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers. Pharmacol Ther 43 539-548, 1988... 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

Renner UD, Oertel R, Kirch W (2005) Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit 27 655-665... 

Stetina PM, Madai B, Kulemann V, Kirch W, Joukhadar C (2005) Pharmacokinetics of scopolamine in serum and subcutaneous adipose tissue in healthy volunteers. Int J Clin Pharmacol Ther 43 134-139... 

Summary. In spite of the sketchy records, BZ appears to be an anticholinergic hallucinogen quite comparable with JB-329 (Dltran) or others of Che JB series or with scopolamine. The onset of effects Is usually rapid, regardless of the route of administration, and the duration Is often a function of the dose. Although pharmacokinetic data on these compounds In man are unavailable, there is some evidence of a dose-response relationship. Without treatment to counter Che effects of these strong central... 

The reactivators of ChE are ordinarily used with cholinolitics and anticonvulsant drugs like diazepam. We studied the pharmacokinetic of HI-6 administrated i.m. to rats alone, with Diazepam and Scopolamin and with them after soman intoxication [14],... 

HI-6 was administrated to rats in dose 36,0 mg/kg b.w. ( l,0xl0-4 M/kg b.w.), Diazepam - 2,5 mg/kg and Scopolamine - 0,5 mg/kg, b.w. administrated i.m. Rats intoxicated with 1,5 LD50 soman (70 pg/b.w., i.m.) were treated 1 min later with drug combination. A HPLC-method for analysis of HI-6 was used. Time-related plasma concentrations were fitted to one-compartment pharmacokinetic model. The result of plasma concentrations are presented in Figure 8 and pharmacokinetics parameters on Table 7. 

This studies are in agreement with our previous studies of HI-6 on cats. The combination of oxime with Scopolamine and Diazepame does not change its pharmacokinetic parameters. The concentration time profile of HI-6 after soman intoxication was shifted to the right. Further investigations have to be carried out with different doses of HI-6 and OPC in order to deepen our understanding of the changes in oxime pharmacokinetics after intoxication (14). 

Dishovsky, C., Ivanov, T., and Samnaliev, I., and Alexandrova, A., Pharmacokinetic of HI-6 combined with diazepam and scopolamine in rats, Toxicology Letters, 123,106,2001. 

J Schnabel, et al. Applications of scopolamine radioreceptor assay to pharmacokinetic studies in rats and humans. Clin Chem 36 1045, 1990. 

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