Five-minute removal of soft lenses prevents most absorption of a topical ophthalmic solution.

PURPOSE: Patients who use topical ophthalmic medications and wear soft contact lenses must remove their lenses before drop instillation to prevent absorption of the medication into the lenses. No previous study has examined how long such a patient should wait before reinserting their lenses. This study was designed to test the hypothesis that waiting 5 minutes before reinsertion of lenses would be sufficient to reduce absorption to a level below what is needed to produce a physiological response. METHODS: Naphcon-A was used as the test solution and pupillary dilation was the physiological response measured. The amount of benzalkonium chloride (BAC) extracted from the lenses was also measured. Twenty-three subjects, none of whom had any significant ocular or systemic abnormalities nor showed pupillary dilation to directly applied Naphcon-A, completed this 3-week study. The study used a 2-period crossover design with a 1-week screening phase. Results were analyzed with a repeated-measure analysis of variance. RESULTS: The pupils averaged 0.316 mm larger when subjects instilled Naphcon-A with lenses in place as compared to when dosing with lenses removed for 5 minutes (P = 0.0008). Nine of 23 subjects showed pupillary dilation greater than 0.5 mm when dosing with lenses in place as compared to none when lenses were removed for 5 minutes. Significantly (P < 0.01) more BAC was extracted from lenses that had been worn during dosing than from lenses removed for 5 minutes (0.9 microgram/lens as compared to no detectible amount). CONCLUSION: Removing soft contact lenses for 5 minutes was sufficient to prevent absorption of clinically significant amounts of Naphcon-A into the lenses.

[The effect of bioadhesiveness of viscous solutions with naphazoline hydrochloride on the elimination of the drug from the eye of swine]. / Einfluss der Bioadhäsivität von Schleimen auf die Elimination von Naphazolinhydrochlorid vom Auge des Hausschweines.

Solutions of sodium carboxymethylamylopectine, tragant, hydroxyethylcellulose, polyvinylalcohol, polyacrylic ester D 339, polyacrylic ester D 340 and polyacrylic acid, all of the same viscosity and with the same concentration of naphazoline hydrochloride, were applied on the isolated eye of pig. After sink the eye in a solution of sodium chloride the elimination of the drug from the eye was investigated. The results were compared with the bioadhesion of the viscous solutions measured ex vivo on the intestine of pigs. There were correlations between the eliminated mass after 5 min, after 30 min and the bioadhesion. Furthermore the calculated initial elimination constant was indirect proportional to the bioadhesion. The elimination of the drug between 5 and 30 min was independent on the bioadhesion.

Disposition of nafimidone in rats.

The absorption, distribution, excretion, and metabolism of 14C-nafimidone, a novel anticonvulsant, have been studied in rats. Nafimidone was completely absorbed following single oral doses of 10 and 100 mg/kg. After both iv and oral administration, nafimidone was rapidly eliminated from plasma (t 1/2 about 5 min), with concomitant formation of a pharmacologically active, nonconjugated metabolite, nafimidone alcohol. Systemic clearance of nafimidone from plasma after iv administration was approximately 2 times higher than hepatic blood flow in rats, and the oral bioavailability was 15%. However, the AUC of nafimidone alcohol was 30% higher after oral administration of nafimidone than that after iv administration of nafimidone. It is likely that, given its pharmacological activity, nafimidone alcohol is the more important species pharmacologically. Distribution of nafimidone-related radioactivity was widespread with highest concentrations associated with liver, kidney, adrenals, and the gastrointestinal tract. Elimination of radioactivity from tissues was rapid and complete, except that retention was noted in arterial vessels and in the ocular melanin of pigmented rats. Determination of hepatic and brain levels of nafimidone and nafimidone alcohol showed no detectable levels of nafimidone in either tissue. However, levels of nafimidone alcohol in liver and brain were as much as 13-fold and 2-fold, respectively, higher than levels in plasma. After either iv or oral administration of 14C-nafimidone, approximately two-thirds of the radioactivity was recovered in urine. The major urinary metabolites of nafimidone after a 100 mg/kg dose were characterized and shown to be dihydroxydihydronaphthalene, substituted nafimidone alcohol, and the 1-beta-glucuronide of nafimidone alcohol.

Inhibition and induction of hepatic drug metabolism in rats and mice by nafimidone and its major metabolite nafimidone alcohol.

Nafimidone, a candidate anticonvulsant agent, and its metabolite (nafimidone alcohol) demonstrated potent inhibition of hepatic drug metabolism in male rats. Inhibition occurred both in vivo following acute administration as a prolongation of hexobarbital sleeping time and as an elevation of plasma hexobarbital levels, and in vitro following addition to hepatic microsomes as a disruption of ethyl-morphine N-demethylation and aniline p-hydroxylation. Inhibition of ethylmorphine N-demethylation was of a mixed type, whereas aniline p-hydroxylation was inhibited in a noncompetitive manner; the micromolar Ki values obtained for both enzymes were severalfold lower than those obtained for imidazole. Nafimidone alcohol produced a type II difference spectrum when added to rat hepatic microsomes. The Ks value was 2.1 microM. Chronic administration of nafimidone alcohol caused induction of hepatic drug metabolism typified by shortening of pentobarbital sleeping time in vivo in male mice and a doubling of hepatic microsomal cytochrome P-450 content in male rats. In rats, these changes were associated with a 30-fold elevation in the Vmax for microsomal ethoxyresorufin O-deethylase and a moderate increase in the Vmax for microsomal ethylmorphine N-demethylase, but no change in either the rate of aniline p-hydroxylation, 4-hydroxybiphenyl- or 4-methylumbelliferone UDP-glucuronosyltransferase, or the activity of the flavoprotein reductase component. These data suggest induction of a predominating cytochrome P-448-type of Phase I drug-metabolizing activity by nafimidone alcohol.