Ephedrine, absorption

Co-administration of ofloxacin and chitosan in eyedrops increased the bioavailabUity of the antibiotic [290]. Trimethyl chitosan was more effective because of its solubility (plain chitosan precipitates at the pH of the tear fluid). On the other hand, N-carboxymethyl chitosan did not enhance the corneal permeability nevertheless it mediated zero-order ofloxacin absorption, leading to a time-constant effective antibiotic concentration [291]. Also W,0-carboxymethyl chitosan is suitable as an excipient in ophthalmic formulations to improve the retention and the bioavailability of drugs such as pilocarpine, timolol maleate, neomycin sulfate, and ephedrine. Most of the drugs are sensitive to pH, and the composition should have an acidic pH, to enhance stability of the drug. The delivery should be made through an anion exchange resin that adjusts the pH at around 7 [292]. Chitosan solutions do not lend themselves to thermal sterilization. A chitosan suspension, however. 

Figure 7 (Left panel) Relative absorption rate for a weak acid (pKa = 3) as a function of mucosal pH for increasing barrier (membrane) permeability (Pb) with fixed unstirred aqueous layer permeability (Pul). X = pHinflectionpoint in Eq. (4). (Right panel) Partition coefficient-dependent absorption rates for salicylic acid and the weak base ephedrine. (From Ref. 19.)...

A spectrophotometric method for determination of primary and secondary amines requires development for each particular compound, determining the kinetics of reaction of the amine with sodium l,2-naphthoquinone-4-sulfonate (143) and the UVV absorption spectrum of the product, under a set of fixed conditions. The procedure was applied to determination of ephedrine (30) and amphetamine (28) in pharmaceutical samples339. Reagent 143 in a FLA. system was used for the fast determination of lysine (144) in commercial feed samples by multivariate calibration techniques, without need of chromatographic separation340. 

Commercial samples containing approximately 400 mg of ephedra per capsule yield roughly 5 mg of ephedrine, 1 mg of pseudoephedrine, and less than 1 mg of methylephedrine (White et al. 1997). For a dose of four capsules, yielding approximately 20 mg of ephedrine, the elimination half-life is 5.2 hours. The time to reach maxium concentration is 3.9 hours. Compared to pure ephedrine tablets, the elimination kinetics of ephedra are comparable. However, ephedra showed somewhat different absorption kinetics (e.g., lag time, area under the concentration-time curve, and maximum plasma concentration). So, ephedra tablets may vary from pure ephedrine in the onset of action, but the durations of action are grossly equivalent. 

Figure 4.8 shows the UV absorption spectrum of a 100 mg/100 ml solution of ephedrine. Ephedrine has the simplest type of benzene ring chromophore, which has a spectrum similar to that of benzene with a weak symmetry forbidden band ca 260 nm with anA (1%, 1 cm) value of 12. Like benzene its most intense absorption maximum is below 200 nm. There are no polar groups attached to or involved in the chromophore so that its vibrational fine structure is preserved because the chromophore does not interact strongly with the solvent. 

Interest in ephedrine in Western medicine was created by the classical investigations of Chen and Schmidt, which began in 1923 as a result of a Chinese druggist s assurance that ma huang was really a potent drug. These workers reported the cardiovascular effects of the alkaloid, its similarity to epinephrine, and its absorption from the intestinal tract. Numerous clinical and experimental studies soon followed, and the use of ephedrine spread so rapidly that several tons of the alkaloid are now consumed yearly. Synthetic ephedrine (racemic) was first prepared in 1927 and marketed under the name Ephetonin (Goodman and Gilman, 1955). 

Ephedrine produces mydriasis when applied locally to the conjunctiva, as well as upon systemic absorption. In humans, there is a striking disparity between the mydriatic effects of ephedrine in Caucasians and in Chinese or blacks. It is most active in the first, less active in the second, and almost completely inactive in the last. The reason for this differential effect on irides of different color has not yet been completely explained. 

Ephedrine is readily and completely absorbed after oral or parenteral administration. As it is less active than epinephrine, it does not produce enough local vasoconstriction to hinder absorption after subcutaneous or intramuscular injection. As has been indicated, ephedrine is resistant to amine oxidase, but it is deaminated to some extent in the liver, probably by the ascorbic-dehydroascorbic acid system. Conjugation also occurs. In addition, up to 40% of the ephedrine administered may be excreted unchanged in the urine. Inactivation and excretion are so slow that the action of ephedrine may persist for several hours. 

Quantum mechanical calculations on the conformational properties of norepinephrine have also been reported. Interconversion of ephedrine and pseudo-ephedrine to a slight extent under y-irradiation has been observed. Absorption of carbon dioxide by cupric ephedrinates can be accounted for by carbamate formation rather than formation of metal-carbon dioxide bonds. -Acylation of /3-phenethylamines by protected amino-acids, e.g. N-CBZ-leucine, has been reported. ... 

Fig. 9. 12. Relationship between absorption rates of salicylic acid and ephedrine and bulk phase pH in the rat small intestine in vivo. Dashed lines represent curves predicted by the pH-partition theory in the absence of an unstirred layer. (From Winne D. The influence of unstirred layers on intestinal absorption in intestinal permeation. In Kramer M, Lauterbach F, eds. Workshop Conference Hoechest, vol 4. Amsterdam Excerpta Medica, 1977 58-64, with permission.)...

Aluminium hydroxide may possibly cause a more rapid onset of pseudoephedrine activity (but this needs confirmation). Any interaction seems unlikely to be clinically significant. Similarly, the effects of kaolin on absorption are small and unlikely to be clinically important. For the effect of sodium bicarbonate on pseudoephedrine and ephedrine, see urinary alka-Iinisers%(p.l277). 

Wilkinson GR, Beckett AH. Absorption, metabolism and excretion of ttie ephedrines inman. 

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