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Biomedical subjects

L Salminen

Publications and source records attributed to L Salminen.

At least 37 records · Page 2Linked to original sources
PubMed1990

Review: systemic absorption of topically applied ocular drugs in humans.

Literature on human plasma concentrations after instillation of ocular timolol, levobunolol, atropine, cyclopentolate, scopolamine, phenylephrine, betamethasone and technetium Tc 99m and theories of lacrimal drainage were reviewed. In all studies the eyedrops absorbed rapidly into the systemic circulation. Like the kinetics of the tracer substances in lacrimal scintigraphy, the plasma drug levels showed interindividual variations. Plasma levels of ocular drugs were lower when punctal occlusion was applied, the mechanism, however, could not be explained. Since an early and a late plasma peak was occasionally registered in some subjects in timolol and cyclopentolate studies, it is suggested that systemic absorption of ocular drugs is low during the nasolacrimal passage but occurs during conjunctival and nasal contact.

Absorption↗
PubMed1990

Systemic absorption of ocular scopolamine in patients.

The systemic absorption of scopolamine 0.25% eyedrops given unilaterally was quantitated in eight patients following therapeutic drug application. Another set of eight patients received placebo drops to study the effect of scopolamine on heart rate, blood pressure and salivation. Scopolamine was rapidly and efficiently absorbed after its ocular administration. The peak plasma scopolamine concentration of 550 +/- 60 pg/ml was reached within 15 minutes in all but two patients. Ocular scopolamine did not affect patients blood pressure or heart rate when compared to patients in the placebo group. Thirty minutes after administration of scopolamine the salivary secretion was slightly but insignificantly reduced.

Absorption↗
PubMed1989

Prevalence of debrisoquine oxidation phenotypes in glaucoma patients.

The oxidation of debrisoquine, a sympatholytic antihypertensive agent, exhibits genetic polymorphism. The debrisoquine/4-OH-debrisoquine metabolic ratio (MR) separates the population to poor (PM, MR greater than 12.6) and extensive (EM, MR less than 12.6) metabolizers. 5-10% of the caucasians belong to the PM phenotype. The oxidation of many other drugs, like timolol, correlates with the debrisoquine phenotype. We determined the debrisoquine phenotype in 102 glaucoma patients. The majority of the patients was treated with ophthalmic timolol. Five patients were classified as PMs. However, two of them were on quinidine, a well known inhibitor of debrisoquine oxidation. The prevalence of debrisoquine PM phenotype in glaucoma patients was 2.9% (excluding patients on quinidine) or 4.9% (with patients on quinidine). The figures are slightly lower than the mean value reported for the normal Finnish population. However, both figures lay within the 95% confidence limits of the prevalence of PM phenotype in the normal Finnish population. The beta-blocking activity of oral timolol is increased in PMs. The significance of timolol oxidation phenotype during ocular timolol therapy warrants further investigation.

Cross-Sectional Studies↗
PubMed1989

Prostaglandin F2 alpha binding to bovine ocular and synthetic melanins in vitro.

The binding of 3H-prostaglandin F2 alpha to bovine iris and synthetic melanin was studied in vitro using a ligand binding assay. Prostaglandin F2 alpha was reversibly bound to both types of melanin. The binding was saturable and the Scatchard analysis revealed the existence of at least two binding sites with the corresponding K(D) values of 3.71 nM and 1.99 microM for natural and 4.99 nM and 0.19 microM for synthetic melanin, respectively. The high affinity Bmax values were 3.4 nM/g for natural and 2.5 nM/g for synthetic melanin. The dissociation of prostaglandin F2 alpha from melanin after dilution of the complex was rapid and uniform.

Animals↗
PubMed1988

Systemic absorption of topically applied ocular atropine.

We quantitated atropine plasma levels and monitored blood pressure, heart rate, and salivary secretion after ocular application. Eight patients received 40 microliters 1% atropine in the lower cul-de-sac of one eye in connection with ocular surgery. Atropine plasma levels were determined for 90 minutes by radioreceptor assay. The peak plasma atropine concentration of 860 +/- 402 pg/ml was reached within 8 minutes in all patients. The ocular absorption of atropine was at least as rapid as that reported for intramuscular administration. Ocular atropine did not affect patients' blood pressure or heart rate when compared with those of the placebo group. Thirty minutes after administration of atropine eyedrops, the salivary secretion in the experimental group was reduced, but was statistically insignificant from the placebo group.

Adult↗
PubMed1988

Timolol binding to bovine ocular melanin in vitro.

The binding characteristics of 3H-timolol to bovine iris melanin were determined by using a ligand binding assay. The association and dissociation kinetics were performed using 100 nM 3H-timolol and 0.5 mg/ml melanin at 37 degrees C. The effects of pH, ethanol, 2.5 microM isoxuprine and 1 microM d- and 1-propranolol on 100 nM 3H-timolol binding were also determined. In saturation experiments 3H-timolol (from 1.25 nM to 5 microM) was equilibrated with 0.5 mg/ml melanin. The binding was saturable with the binding maximum of about 1 microM timolol/g melanin. The binding of 100 nM 3H-timolol to melanin increased up to 5 hours and amounted 24% of the added radioactivity. The best fit of the association constants was obtained by using a two fit model. The association rate constants were 4.92 x 10(5) M-1 min-1 and 5.95 x 10(6) M-1 min-1. The dissociation was rapid in vitro and uniphasic with a dissociation rate constant of 5.08 x 10(-3) min-1. The pH, ethanol and both enantiomers of propranolol did not appreciably alter the timolol binding, while isoxuprine diminished it.

Animals↗
PubMed1987

The pharmacokinetics of ocularly applied timolol in rabbits.

[3H]timolol derived radioactivity and beta-antagonistic activity in the aqueous humour, iris, ciliary body and blood in rabbits were analyzed by liquid scintillation counting (LSC) and radioreceptor assay (RRA) after ocular timolol. After ocular application of tracer labelled timolol, the radioactivity decreased slowly in the iris (Kel = 0.05 h-1) and ciliary body (Kel = 0.02 h-1). In the aqueous humour the elimination rate was faster (Kel = 0.57 h-1). The beta-antagonistic activities of the aqueous humour and plasma decreased rapidly when compared to LSC values. The ethanol extractable pool of the beta-antagonistic activity from the iris and ciliary body was only a few percent of the corresponding LSC estimates. The kinetics of beta-antagonistic activity extractable from iris and ciliary body was identical with that in the aqueous humour. Timolol concentrations in the untreated rabbit eye were sufficiently high to lower the intraocular pressure.

Animals↗
PubMed1986

Effects of eyelid closure and nasolacrimal duct occlusion on the systemic absorption of ocular timolol in human subjects.

Eyelid closure and nasolacrimal occlusion may decrease the systemic absorption of topically applied drugs. We studied the absorption kinetics of 20 microliter 0.5% timolol eyedrops in eight healthy volunteers. Each subject was supine for 30 minutes after the drug application. In randomized order, the volunteers kept their eyelids closed (ELC), or applied nasolacrimal occlusion (NLO) or blinked normally. Blood samples were drawn up to 90 minutes and analyzed for timolol with a radioreceptor assay. There was great interindividual variation in the timolol absorption. NLO reduced the total timolol absorption, but in some subjects the initial absorption was also enhanced by this procedure.

Absorption↗
PubMed1985

Systemic absorption of topically applied ocular timolol.

Symptoms and findings arising from the systemic beta blockade caused by topical ocularly applied timolol appear shortly after drug application. We studied the systemic absorption of 20 microliters of 0.5% timolol instilled unilaterally in the lower conjunctival cul-de-sac in 6 volunteers. At 3 min one subject, at 5 min three and at 8 min all but one showed measurable (greater than or equal to 215 pg/ml) timolol concentrations in the plasma. The rapid systemic absorption of topically applied ocular timolol observed in our study is consistent with the rapid appearance of the cardiovascular and pulmonary side effects reported in connection with timolol eye drop therapy.

Adult↗
PubMed1985

A comparison between iris-ciliary body concentration and receptor affinity of timolol.

Topical unilateral application of timolol reduces the IOP (intraocular pressure) of both the treated and the untreated eye. For this reason, a cental mechanism of action, in addition to the local one, has been suggested for the reduction of IOP by this drug. In this study timolol concentrations in the iris-ciliary body of the treated and untreated rabbit eyes were compared with pharmacologically active in vitro timolol concentrations. The drug concentration in the untreated eye too was found to be high enough to exert a local action.

Animals↗
PubMed1985

Transient corneal anaesthesia after topical pindolol in rabbits.

The acute corneal anaesthetic potency of 0.5% pindolol eye drops was compared with that of 2% lidocaine and placebo solutions in 10 rabbits. Pindolol produced a rapid-onset anaesthetic effect similar to that of lidocaine, whereas placebo drops were without effect. The chronic effect of 0.25% pindolol, 0.5% timolol and placebo eye drops on corneal sensitivity were evaluated weekly for 1 month in rabbits. None of the solutions affected the basal corneal sensitivity, but pindolol eye drops caused a slight corneal anaesthesia, when tested at 10 min after application, especially during the first weeks of therapy. The effect of timolol was qualitatively similar, but much weaker and not statistically significant.

Anesthetics, Local↗
PubMed1985

Concentration-dependent precorneal loss of pilocarpine in rabbit eyes.

Precorneal loss of pilocarpine was studied in pigmented and albino rabbits. We instilled 25 microliter of isotonic pilocarpine solution, pH 6.4, into rabbit eyes and monitored drug concentration in the precorneal tear film. Increased concentration (0.2% - 2.0%) of pilocarpine accelerated precorneal drug loss from the tear film from 0.686 min-1 to 1.064 min-1. This increase was mainly due to induced lacrimation. Polyvinyl alcohol (1.4%) retarded precorneal loss of pilocarpine. The rate of loss was the same in pigmented and albino rabbits. The effects of the changed precorneal loss of pilocarpine on corneal drug absorption are discussed.

Animals↗
PubMed1985

The effect of ocular pigmentation on intraocular pressure response to timolol.

The one-hour intraocular pressure (IOP) response to topical ocularly applied timolol was studied in darkly and lightly pigmented eyes. One drop of 0.25% 1-timolol was applied to one eye of ten subjects with brown and ten subjects with blue iris color. In the treated and untreated eyes with blue iris color the IOP fell significantly from the baseline value, whereas no pressure reduction was obtained either in the treated or untreated eyes with brown iris color. Beta-blocking agents are known to accumulate in pigment-containing ocular structures. The lack of a one-hour pressure response to timolol in darkly pigmented eyes observed in our study may refer to the reduction of 1-timolol in the biophase due to excessive pigment binding.

Adult↗