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At least 37 records · Page 2Linked to original sources
PubMed1991

Effects of topical administration of timolol maleate on intraocular pressure and pupil size in cats.

Effects of topical administration of a single dose of timolol maleate, a nonselective beta-adrenergic blocking agent, on intraocular pressure (IOP) and pupil diameter were evaluated in the normotensive eyes of 10 clinically normal cats over 12 hours. Mean (+/- SEM) normal IOP was 17.1 (+/- 1.1) mm of Hg and diurnal fluctuation was observed, with the highest IOP seen in the evening. Mean (+/- SEM) normal pupil diameter was 10.1 (+/- 0.5) mm. Topical treatment with 0.5% timolol resulted in reduction of IOP in treated and nontreated eyes. This effect was time-dependent and was first observed at 6 hours after treatment. Mean reduction of IOP was 22.3% in the treated eye and 16.3% in the nontreated eye. The treated eye had reduced pupil diameter at 30 minutes after treatment, and miosis persisted throughout the 12 hours of the study. Mean reduction of pupil diameter was 38.7%. A contralateral effect on pupil diameter was not seen in the nontreated eye. Topical administration of timolol maleate results in a reduction of IOP in treated and contralateral eyes, which supports the use of timolol for treatment of glaucoma in cats. In addition, the treated eye becomes miotic. This effect may indicate beta-adrenergic inhibition or alpha-adrenergic activation of the iris sphincter muscle. beta-Adrenergic blockade would then result in miosis.

Administration, Topical↗
PubMed1999

Pharmacokinetics of latanoprost in the cynomolgus monkey. 1st communication: single intravenous, oral or topical administration on the eye.

Latanoprost (13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2a- isopropyl ester, CAS 130209-82-4 PhXA41, Xalatan) is a prodrug used for reduction of the intraocular pressure in the treatment of glaucoma. The pahrmacokinetics of this drug was studied in the cynomolgus monkey after intravenous, oral and topical administration of 9 beta-[3H] labelled latanoprost. The plasma profile of radioactivity from HPLC separation of samples obtained after intravenous as well as topical administration on the eyes showed a rapid and complete hydrolysis of the ester. The pharmacologically active acid of latanoprost showed a maximum concentration 5 min post topical administration and an elimination half-life of about 10 min. Tertiary butyldimethylsilyl derivatives were prepared of the radioactive fractions collected from the HPLC column. The derivatives were analysed by gas chromatography-mass spectrometry (GC-MS). After oral administration no latanoprost and very little of its acid was present in plasma, indicating a first-pass metabolism resulting in more polar compounds. Based on the retention times on the HPLC and GC and on a mass spectrum similar to the acid of latanoprost but 28 daltons lower, the main metabolite in urine and faeces was identified as the 1,2-dinor acid of latanoprost. In a similar way a more polar fraction from urine was identified as the 1,2,3,4-tetranor metabolite of the acid of latanoprost. The tissue distribution after i.v. and topical administration was similar with organs of metabolism (liver) and elimination (kidney) containing the highest concentrations. After topical application much of the dose was found in the anterior ocular tissues but not in the posterior parts of the eye. In conclusion, latanoprost is a prodrug which in vivo rapidly is hydrolysed to the corresponding free acid. The acid of latanoprost has a short half-life in plasma and is extensively metabolised mainly through beta-oxidation before it is excreted into the urine and faeces.

Administration, Oral↗
PubMed1996

Inhibitory effect of the topical administration of a bisphosphonate (risedronate) on root resorption incident to orthodontic tooth movement in rats.

Root resorption associated with tooth movement is an unsolved problem in orthodontics. If such root resorption could be prevented, it would be an important contribution toward reducing risk factors in orthodontic treatment. The purpose of this study was to examine the effects of the topical administration of a bisphosphonate, risedronate, which is known to be a potent blocker of bone resorption, on root resorption during tooth movement and on the repair of the resorbed root surface after tooth movement in rats. In the first experiment, both the right and left upper first molars were moved buccally with a standardized expansion spring under administration of risedronate. After day 7, extensive root resorption had occurred on the control side, and the area of root resorption reached a maximum on day 14. The topical administration of risedronate caused a significant and dose-dependent inhibition of root resorption after the orthodontic force was applied. In the second experiment, the right and left upper molars were first moved buccally for 3 weeks. Risedronate treatment began on the day the spring was removed. After the force was withdrawn, the resorbed root surfaces on both the control and risedronate-treated sides were gradually restored by apposition of repair cementum (cementoid). The topical administration of risedronate did not appear to inhibit the repair process of root resorption. These results suggest that the topical administration of risedronate may be useful in preventing root resorption of teeth during orthodontic treatment.

Administration, Topical↗
PubMed1997

Topical administration of racemic ibuprofen.

In vitro experiments to investigate possible stereoselective aspects of the topical administration of ibuprofen have been conducted. Incubation of ibuprofen with rat skin homogenates in the presence of coenzyme A, ATP, and magnesium provided no evidence for the formation of ibuprofenyl coenzyme A (the initial intermediate in the metabolic inversion of [R]- to [S]-ibuprofen). Similar incubation studies gave no indication of a change in the enantiomeric ratios of ibuprofen over the time course of the experiments. Percutaneous penetration studies of ibuprofen gel through porcine skin indicated that the ibuprofen enantiomer levels in the reservoir solutions were consistent with racemic ibuprofen having traversed the skin with no metabolic inversion. These results suggest that, in the models studied, skin metabolism does not result in the chiral inversion of (R)- to (S)-ibuprofen and that the topical administration of ibuprofen will result in the delivery of 50% "isomeric ballast."

Administration, Topical↗
PubMed1994

Effect of topical administration of glucose on neurons innervating abdominal viscera in dorsal motor nucleus of vagus in rats.

Neural responses in the dorsal motor nucleus of the vagus (DMV) to topical administration of glucose were investigated electrophysiologically using multibarrel electrodes in anesthetized rats. Of 52 neurons that showed the antidromic response to the ventral gastric vagus, 4 neurons increased and 14 neurons decreased their discharge rates in response to topical administration of glucose from the multibarrel pipette. Thirty-four neurons did not respond to this administration. Of 4 neurons that showed the antidromic response to the accessory celiac vagus, 1 neuron increased and 1 neuron decreased their discharge rates in response to topical administration of glucose. Two neurons did not respond to this administration. These results suggest that some DMV neurons innervating the abdominal viscera may have an enteroceptor function detecting the change in glucose concentration of their environment.

Administration, Topical↗
PubMed1999

Pharmacokinetics of latanoprost in the cynomolgus monkey. 2nd communication: repeated topical administration on the eye.

Latanoprost (13,14-dihydro-15(R)-17-phenyl-18,19,20-trinor-PGF2a isopropyl ester, CAS 130209-82-4 PhXA41, Xalatan) is an antiglaucoma prodrug which enhances the bioavailability of the drug into the eye compared to the corresponding acid. The pharmacokinetics and metabolism of this drug was studied in the cynomolgus monkey after daily topical administration on the eye of [13,14-(3) H] labelled latanoprost (6 micrograms per eye) during 21 days. Plasma, urine and homogenised faeces samples were purified by separation on a Sep-Pak C18 cartridge before analysis by reversed phase liquid chromatography (RP-HPLC) with one-line radioactivity detection. The maximum plasma concentration of radioactivity obtained within 10 min post dose was as a mean 7.87 +/- 3.18 ng eq./ml on day 1 and 9.31 +/- 4.21 ng eq./ml on day 21. The plasma concentration of radioactivity declined rapidly up to 3 h post-dose both on day 1 and day 21, but a small amount of tritiated water accumulated with time. The majority of the radioactivity was recovered in urine but substantial amounts were also eliminated in the faces. No latanoprost was found in plasma after repeated topical administration on the eye. The plasma profiles from HPLC separation of samples showed a rapid and complete hydrolysis of the ester. The elimination half-life of the acid of latanoprost was estimated to be 13.8 +/- 1.7 min for day 1 and 12.4 +/- 4.8 min for day 21. No induction or inhibition of the metabolism occurred after the repeated administration. By comparison with reference substances the 15-keto acid of latanoprost was found to be present in plasma and the major metabolites in urine and faeces collected during day 2 and day 20 were identified as 1,2-dinor acid of latanoprost, 1,2,3,4-tetranor acid and 1,2,3,4-tetranor lactone of latanoprost. Tritiated water was excreted in the urine and a small amount of the acid of latanoprost was excreted in the faeces. In conclusion, latanoprost was rapidly absorbed and hydrolysed to the corresponding acid after repeated topical administration to the monkey eye. The acid of latanoprost had a short half-life in plasma and it was partly converted to the 15-keto acid of latanoprost. beta-Oxidation of the acid of latanoprost was the major metabolic pathway. No induction or inhibition of the metabolism occurred upon repeated administration and no indications of accumulation of the drug or drug metabolites were observed. The pharmacokinetics of latanoprost was similar after a single and repeated topical administration.

Administration, Topical↗
PubMed1998

Comparison of topical administration of clotrimazole through surgically placed versus nonsurgically placed catheters for treatment of nasal aspergillosis in dogs: 60 cases (1990-1996).

OBJECTIVE: To examine the clinical response to topical administration of clotrimazole in dogs with nasal aspergillosis, to compare effect of surgically placed versus nonsurgically placed catheters used for administration on outcome, and to examine whether subjective scoring of computed tomographic images can predict outcome. DESIGN: Retrospective case series. ANIMALS: 60 dogs with nasal aspergillosis. PROCEDURE: Information including signalment, history, diagnostics, treatment method, and outcome was retrieved from medical records of dogs with nasal aspergillosis treated between 1990 and 1996 at the University of California School of Veterinary Medicine or cooperating referral practices. Final outcome was determined by telephone conversations with owners and referring veterinarians. Images obtained before treatment were subjectively assessed to develop an algorithm for predicting outcome. RESULTS: Clotrimazole solution (1%) was infused during a 1-hour period via catheters surgically placed in the frontal sinus and nose (27 dogs) and via nonsurgically placed catheters in the nose (18). An additional 15 dogs received 2 to 4 infusions by either route. Topical administration of clotrimazole resulted in resolution of clinical disease in 65% of dogs after 1 treatment and 87% of dogs after one or more treatments. The scoring system correctly classified dogs with unfavorable and favorable responses 71 to 78% and 79 to 93% of the time, respectively. CLINICAL IMPLICATIONS: Topical administration of clotrimazole, using either technique, was an effective treatment for nasal aspergillosis in dogs. Use of non-invasive intranasal infusion of clotrimazole eliminated the need for surgical trephination of frontal sinuses in many dogs and was associated with fewer complications.

Administration, Intranasal↗
PubMed1991

Reduced severity of oxygen-induced retinopathy in the newborn rat after topical administration of timolol maleate. A preliminary study.

The effects of timolol maleate on intraocular pressure (IOP) and the severity of retinopathy induced by exposure to 80% oxygen were studied in newborn Wistar rats. One drop of timolol maleate (0.25%) instilled in each eye twice a day for the first ten days of life substantially reduced intraocular pressure without significantly modifying arterial pressure. Forty percent of the ratlings treated in this way failed to develop oxygen-induced retinopathy (OIR) after exposure to 80% oxygen for the first five days of life; in the other 60% OIR was less severe than that seen in an identically oxygenated group that did not receive timolol. The authors hypothesize that the pharmacologically induced reduction in IOP may have attenuated the effects of the high concentrations of oxygen on the immature retinal vessels by improving the ocular perfusion pressure. The possibility that timolol maleate also exerts a direct action on the caliber of these vessels cannot be excluded.

Administration, Topical↗
PubMed1981

Whole-body autoradiography after systemic and topical administration of methyl acrylate in the guinea pig.

Whole-body autoradiography was performed in the guinea pig with methyl (2,3-14C)-acrylate. Radioactive material quickly disappeared from the body after oral and, somewhat slower, after i.p. administration for the greater part. After administration in a closed cup on the skin a slow penetration in the dermis occurred preceded by the toxic effect, mainly a strong edema. In the first 16 h metabolism was primarily restricted to the skin, internal organs showed a slow rise in radioactivity. A large part of the labeled material was retained in the dermis. The detoxification was screened by estimating the urinary thioether content and respiratory carbon dioxide. This showed that in addition to oxidation to carbon dioxide the binding to SH-groups was the principal way of metabolism.

Acrylates↗
PubMed1988

Effect of topical administration of vancomycin versus chlorhexidine on alpha-hemolytic streptococci in oral cavity.

In a crossover study the effect of local vancomycin (paste containing 0.5% vancomycin applied to the gums three times a day for 7 days) versus chlorhexidine mouth rinsing (0.2% chlorhexidine solution twice a day for 7 days) on alpha-hemolytic streptococci in the oral cavity was investigated in eight volunteers. Mixed saliva and dental plaque samples were collected for microbiologic analysis before administration, during treatment, and after withdrawal of the agents. The numbers of different alpha-hemolytic streptococci were determined in the samples. The total numbers of Streptococcus mitior, Streptococcus mutans, and Streptococcus sanguis were significantly reduced by the vancomycin treatment compared with the chlorhexidine treatment (p less than 0.05) after 2 days of administration. Two days after the treatment was stopped the numbers of alpha-hemolytic streptococci had returned to pretreatment levels. Local prophylaxis with vancomycin as a complement to systemic antimicrobial prophylaxis may therefore be useful in the prevention of infective endocarditis.

Administration, Topical↗