Biomedical subjects

A Bozkurt

Publications and source records attributed to A Bozkurt.

At least 37 records · Page 2Linked to original sources

PubMed2000

Penetration of topical and oral ofloxacin into the aqueous and vitreous humor of inflamed rabbit eyes.

PURPOSE: This study aimed to investigate the penetration of topical and oral ofloxacin into aqueous humor and vitreous humor in post-traumatic endophthalmitis model in rabbits. METHODS: A standardized intraocular infection after penetrating injury was made in the right eyes of 16 rabbits. Intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes were maintained as controls. The animals were divided randomly into two groups. (1) In the topical group, two drops of ofloxacin 0.3% eyedrops were instilled to both eyes every 30 min for 4 h. (2) In the topical-oral group, two doses of 25 mg/kg of ofloxacin at 12-h intervals were given orally, then the protocol of the first group was applied. Aqueous and vitreous humor samples were taken 30 min after the last drop. Ofloxacin concentrations were measured by using HPLC. RESULTS: Mean aqueous levels of ofloxacin in control eyes were: 3.25 +/- 2.55 microg/ml in topical group. 4.58 +/- 5.39 microg/ml in topical-oral group. Mean aqueous levels in inflamed eyes were: 5.21 +/- 4.55 microg/ml in topical group, 10.34 +/- 8.88 microg/ml in topical-oral group. Mean vitreous levels of ofloxacin in control eyes were: 0.17 +/- 0.07 microg/ml in topical group, 1.30 +/- 1.23 microg/ml in topical-oral group. Mean vitreous levels in inflamed eyes were: 0.35 +/- 0.22 microg/ml in topical group, 3.48 +/- 2.69 microg/ml in topical-oral group. There was no significant difference among the groups (P > 0.05), however. CONCLUSIONS: The result of this study suggests that oral supplementation of ofloxacin to topical instillation increased the ocular levels of ofloxacin in the post-traumatic endophthalmitis model. Mean drug concentrations in aqueous and vitreous humors were above the 90% minimum inhibitory concentrations (MIC90) for most of the common microorganisms causing endophthalmitis in all eyes, except in the vitreous humors of the intact eyes instilled topically.

Administration, Topical↗

PubMed2000

The effects of prolonged acute use and inflammation on the ocular penetration of topical ciprofloxacin.

PURPOSE: To study the aqueous and vitreous penetration of ciprofloxacin after prolonged acute topical administration and to investigate the effects of inflammation on drug penetration. METHODS: A standardized model of intraocular infection after penetrating injury was made in the right eyes of eight rabbits. The intact left eyes were maintained as the control. Two drops of ciprofloxacin 0.3% eyedrops were instilled topically every 1 h for 7 h to all eyes of the rabbits. Aqueous and vitreous samples (100 microl) were obtained half an hour after the last drop. Instillation was continued for 7 h more and samples were obtained as before. Drug concentrations were measured using HPLC. RESULTS: The mean aqueous humor levels of ciprofloxacin were: in control eyes 1.31 +/- 0.78 microg/ml after 7 h and 1.85 +/- 1.69 microg/ml after 14 h of instillation: in inflamed eyes 2.18 +/- 1.02 microg/ml after 7 h and 2.91 +/- 2.12 microg/ml after 14 h. The mean vitreous humor levels were: in control eyes 0.65 +/- 0.44 microg/ml after 7 h and 0.72 +/- 0.8 microg/ml after 14 h of instillation; in inflamed eyes 0.67 +/- 0.77 microg/ml after 7 h and 1.01 +/- 0.43 microg/ml after 14 h. However, the differences among the groups were not significant (P > 0.05). CONCLUSIONS: Ciprofloxacin penetration into aqueous humor was higher in 14-h topical application than that for 7 h. Inflammation increased the penetration of topical ciprofloxacin into aqueous while administered for 7 h and into both aqueous and vitreous humor while administered for 14 h. c

Administration, Topical↗

PubMed2000

Cefaclor, a cephalosporin antibiotic, delays gastric emptying rate by a CCK-A receptor-mediated mechanism in the rat.

Studies in vitro suggest that cephalosporin antibiotics release the gut hormone cholecystokinin. Cholecystokinin is known to inhibit gastric emptying. Here we examine the effects of cefaclor on gastric emptying and intestinal motility. Male Sprague-Dawley rats were fitted with gastric cannulas. Following a 3-week recovery, the rate of gastric emptying of saline, peptone (4.5%) or cefaclor was determined after instillation into the gastric cannula, while intestinal transit was measured by using the propagation of arabic gum + charcoal mixture given intraduodenally. Gastric emptying of saline was significantly delayed by the addition of cefaclor (3, 10, 30 or 100 mM). The CCK-A antagonist SR-27897B (1 mg kg(-1), i.p.) reversed the delay induced by 10 mM cefaclor, whereas the CCK-B antagonist CI-988 (1 mg kg(-1), i.p.) had no significant effect. In capsaicin-treated rats, 10 mM cefaclor emptied more rapidly than in vehicle-treated animals. Thirty-minute intestinal transit was increased at 30 and 100 mM of cefaclor, while the gastric acid secretion following cefaclor instillation was no different than the group which received saline. The cephalosporin antibiotic cefaclor appears to be a potent stimulant of CCK release from gut endocrine cells, resembling the effects of peptone. Cefaclor delays gastric emptying via capsaicin-sensitive afferent pathways, which involve CCK-A receptor interaction.

Animals↗

PubMed2000

Fluence-to-dose conversion coefficients from monoenergetic neutrons below 20 MeV based on the VIP-man anatomical model.

A new set of fluence-to-absorbed dose and fluence-to-effective dose conversion coefficients have been calculated for neutrons below 20 MeV using a whole-body anatomical model, VIP-Man, developed from the high-resolution transverse colour photographic images of the National Library of Medicine's Visible Human Project. Organ dose calculations were performed using the Monte Carlo code MCNP for 20 monoenergetic neutron beams between 1 x 10(-9) MeV and 20 MeV under six different irradiation geometries: anterior-posterior, posterior-anterior, right lateral, left lateral, rotational and isotropic. The absorbed dose for 24 major organs and effective dose results based on the realistic VIP-Man are presented and compared with those based on the simplified MIRD-based phantoms reported in the literature. Effective doses from VIP-Man are not significantly different from earlier results for neutrons in the energy range studied. There are, however, remarkable deviations in organ doses due to the anatomical differences between the image-based and the earlier mathematical models.

Algorithms↗

PubMed2000

The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats.

BACKGROUND: Taurine, which is the major intracellular free beta-amino acid, is known to be an endogenous antioxidant and a membrane-stabilizing agent. In this study, we wished to know whether taurine altered the concentration of gentamicin in kidney tissue and could protect against gentamicin-induced acute proximal tubular injury. METHODS: Wistar albino rats of both sexes were assigned to three groups, which all received one of the following daily intraperitoneal injections for 8 days: (i) 0.9% sodium chloride (NaCl) alone at the same volume as gentamicin treated rats (group C; n=8); (ii) 100 mg/kg/day gentamicin alone (group G; n=8, four male, four female); or (iii) 100 mg/kg/day gentamicin plus 7.5 ml/kg/day taurine (group G+T; n=9, five male, four female). Urine was collected for 24 h for the determination of urine volume and creatinine. Intracardiac blood was collected for blood urea nitrogen (BUN) and serum creatinine determination. The kidneys were removed, weighed, and the left kidneys were subjected to biochemical analysis for the determination of thiobarbituric acid-reactive substance (TBARS) and lactate levels, and glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities. The right kidneys were divided vertically in half. The upper halves were used for histopathological examination, by light and electron microscopy. The lower halves were used to detect the gentamicin concentration within the kidney tissue, by high-performance liquid chromatography (HPLC). Changes in body weight and normalized kidney weight were recorded. RESULTS: Taurine treatment reduced gentamicin-induced increases in serum creatinine, 24 h urine volume, BUN and tissue lactate and TBARS levels (0.57+/-0.02 vs 1.06+/-0.08 mg/dl, P<0.001; 9.00+/-1.46 vs 20.9+/-2.73 ml, P<0.001; 25.3+/-1.87 vs 54.1+/-6.99 mg/dl, P<0. 001; 2.56+/-0.10 vs 3.44+/-0.08 micromol/g wet tissue, P<0.001; and 66.4+/-3.41 vs 79.5+/-5.07 nmol/g wet tissue, P>0.05, respectively). Taurine reduced the accumulation of gentamicin within the kidney tissue (233+/-29 vs 494+/-93 microg/g wet tissue, P<0.05). Taurine treatment also prevented body weight loss due to gentamicin administration (17.8+/-1.64 vs -10.0+/-7.08 g, P<0.01) and normalized reduced Gpx and SOD activities (3.46+/-0.16 vs 2.37+/-0. 15 U/g wet tissue, P<0.01; and 15577+/-377 vs 12662+/-577 U/g wet tissue, P<0.01, respectively). Light microscopic examination of the renal tissues from gentamicin-treated rats revealed severe histopathological changes, whereas specimens obtained from taurine-treated rats revealed only mild changes. This finding was supported by electron microscopic examination. CONCLUSIONS: Our observations suggest that taurine treatment attenuates the accumulation of gentamicin within kidney tissue and counteracts the deleterious effect of gentamicin on renal tubular function. They may have potentially important clinical implications.

Acute Disease↗

PubMed2000

VIP-Man: an image-based whole-body adult male model constructed from color photographs of the Visible Human Project for multi-particle Monte Carlo calculations.

Human anatomical models have been indispensable to radiation protection dosimetry using Monte Carlo calculations. Existing MIRD-based mathematical models are easy to compute and standardize, but they are simplified and crude compared to human anatomy. This article describes the development of an image-based whole-body model, called VIP-Man, using transversal color photographic images obtained from the National Library of Medicine's Visible Human Project for Monte Carlo organ dose calculations involving photons, electron, neutrons, and protons. As the first of a series of papers on dose calculations based on VIP-Man, this article provides detailed information about how to construct an image-based model, as well as how to adopt it into well-tested Monte Carlo codes, EGS4, MCNP4B, and MCNPX.

Adult↗

PubMed2000

Subretinal fluid levels of topical, oral, and combined administered ciprofloxacin in humans.

AIMS: To investigate the subretinal fluid (SRF) penetration of ciprofloxacin following topical, oral, and combined administration. METHODS: 34 patients undergoing conventional retinal reattachment surgery were randomly assigned to three groups. Twelve patients received topical ciprofloxacin, 11 patients received oral ciprofloxacin, and the other 11 patients received combined drug administration. SRF drug level was measured by using high performance liquid chromatography method. RESULTS: The highest drug concentrations of all tested modes were attained following combined administration and lowest following topical administration (p<0.001). The SRF drug concentration following oral administration was also significantly higher than that of topical administration (p<0.001). Concentrations after oral and combined administration did not differ significantly (p = 0.217). CONCLUSIONS: Topical ciprofloxacin can penetrate SRF. Ocular bioavailability of ciprofloxacin in SRF after oral and combined administration is equivalent.

Adult↗

PubMed2000

Glucagon-like peptide (GLP-1) is involved in the central modulation of fecal output in rats.

In addition to its insulinotropic action, exogenously administered glucagon-like peptide (GLP-1) inhibits gastropancreatic motility and secretion via central pathways. The aims of the present study were to evaluate the effects of exogenous GLP-1-(7-36) amide on fecal output and to investigate the role of endogenous GLP-1 on stress-induced colonic activity. With the use of a stereotaxic instrument, adult male Sprague-Dawley rats weighing 200-250 g were fitted with stainless steel cerebroventricular guide cannulas under ketamine anesthesia. A group of rats were placed in Bollman-type cages to induce restraint stress. Fecal output monitored for 2 h was increased significantly by intracerebroventricular GLP-1 to 500, 1, 000, and 3,000 pmol/rat (P < 0.05-0.01), whereas intraperitoneal GLP-1 had no effect. Intracerebroventricular administration of the GLP-1 receptor antagonist exendin-(9-39) (10 nmol/rat) reversed the increases induced by GLP-1 (500 pmol/rat; P<0.01). Similar results were also observed with the injection of corticotropin-releasing factor receptor antagonist astressin (10 microg/rat icv). The significant increase in fecal pellet output induced by restraint stress was also decreased by both intracerebroventricular exendin (10 nmol/rat) and astressin (10 microg/rat; P<0.01-0.001). These results suggest that GLP-1 participates in the central, but not peripheral, regulation of colonic motility via its own receptor and that GLP-1 is likely to be a candidate brain-gut peptide that acts as a physiological modulator of stress-induced colonic motility.

Animals↗

PubMed2000

Endothelin-1-induced PMN infiltration and mucosal dysfunction in the rat small intestine.

The objectives of this study were to characterize the effects of endothelin (ET)-1 on intestinal mucosal parameters and to assess the contribution of polymorphonuclear leukocytes (PMNs), intercellular adhesion molecule-1 (ICAM-1), and a platelet-activating factor (PAF) to the mucosal dysfunction induced by ET-1. Different concentrations of ET-1 (100, 200, and 400 pmol/kg) were infused into the superior mesenteric artery for 10 min, and tissue samples were obtained 30 min after terminating the infusion. ET-1 administration significantly elevated tissue myeloperoxidase activity, plasma carbonyl content, and tissue chemiluminescence intensity, indicating that ET-1 produces PMN infiltration and oxidant stress. Blood-to-lumen clearance of (51)Cr-EDTA significantly increased after ET-1 infusion (400 pmol/kg). Monoclonal antibodies against ICAM-1 (1A29, 2 mg/kg), antineutrophil serum, and PAF antagonist (WEB-2086, 10 mg/kg) attenuated the mucosal barrier dysfunction induced by ET-1. Overall, our data indicate that ET-1 causes PMN accumulation, oxidant stress, and mucosal dysfunction in the rat small intestine and that ET-1-induced mucosal dysfunction involves a mechanism that includes a role for PMNs, ICAM-1, and PAF.

Animals↗

PubMed2000

Association between idiopathic mitral valve prolapse and panic disorder.

AIM: To evaluate the association between idiopathic mitral valve prolapse and panic disorder. METHODS: The study comprised 50 patients with idiopathic mitral valve prolapse, 50 patients with panic disorder, and 50 healthy controls. All subjects underwent echocardiographic evaluation. If idiopathic mitral valve prolapse was present, the level of prolapse was measured. To reach psychiatric diagnosis, the Structured Clinical Interview for DSM-IV Axis I Disorders, clinician version, was administered to all subjects. For psychometric evaluation, all subjects completed the Symptom Check List, Beck Depression Inventory, and State and Trait Anxiety Inventory. RESULTS: The prevalence of panic disorder was 16% in patients with idiopathic mitral valve prolapse, and 2% in healthy controls (p=0.03). The average scores on all psychometric scales were the highest in the panic disorder group, whereas average scores in idiopathic mitral valve prolapse group were significantly higher than in the control group (p<0.001). Idiopathic mitral valve prolapse and panic disorder groups displayed similar features of panic attack symptoms. Panic disorder cases with idiopathic mitral valve prolapse and those without it did not significantly differ in terms of psychometric evaluations and clinical symptoms. CONCLUSION: The possibility of comorbidity of panic disorder and idiopathic mitral valve prolapse should be taken into account in the approach to the patients diagnosed with either of the disorders.

Adolescent↗

PubMed1999

Capsaicin-sensitive vagal fibres and 5-HT3-, gastrin releasing peptide- and cholecystokinin A-receptors are involved in distension-induced inhibition of gastric emptying in the rat.

The present study was undertaken to investigate how the activation of gastric mechanoreceptors by distension of the stomach in conscious gastric fistula rats influences gastric emptying; and the roles of capsaicin sensitive vagal afferent fibres and the 5-HT3, GRP and CCK-A receptors involved in mediating these responses. To activate mechanoreceptors by non-nutrient dependent pathways, methylcellulose in saline was used to distend the stomach (5 cm H2O) and the subsequent emptying of saline was examined immediately, and at 3, 5 and 10 min following distension. Prior distension delayed the subsequent emptying of saline instilled into the stomach compared with non-distended controls (2.28+/-0.09 ml/5 min; P < 0.001). Topical application of capsaicin, completely abolished the distension-induced inhibition of gastric emptying when compared with vehicle treated rats (2.82+/-0.09 vs. 2.38+/-0.04 ml/5 min; P < 0.001). Peripheral administration of a GRP antagonist (2258 U89UJ, 1 mg/kg), and a 5-HT3 antagonist (BRL4369UA, 50 microg/kg) significantly reversed (2.56+/-0.14 ml/5 min; P < 0.05 and 2.61+/-0.07 ml/5 min; P < 0.01; respectively) the delay in gastric emptying induced by distension. When the rats were treated with the CCK-A antagonist, gastric emptying of saline following distension was also significantly facilitated (2.56+/-0.07 ml/5 min; P < 0.001). In contrast, the CCK-B/gastrin receptor antagonist had no significant effect on the distension induced delay in gastric emptying (1.95+/-0.12 ml/5 min). The present results suggest that gastric distension in conscious gastric fistula rats delays gastric emptying by activating capsaicin-sensitive extrinsic afferent nerve fibres. Moreover, the results also indicate that distension-induced mechanisms involve GRP, 5-HT3 and CCK-A receptors, but not CCK-B receptors.

Animals↗

PubMed1999

CYP2D6 polymorphism in systemic lupus erythematosus patients.

OBJECTIVES: To determine whether patients with idiopathic systemic lupus erythematosus (SLE) are associated with impaired CYP2D6 activity and to gain insight into whether there is an association between particular CYP2D6 genotypes and susceptibility to SLE, and whether CYP2D6 polymorphism is linked to any specific clinical features of SLE. METHODS: Debrisoquine sulfate (10 mg p.o.) was given to 159 healthy volunteers and 39 idiopathic SLE patients. Genotypic assay was carried out in 80 healthy volunteers and 32 patients. A 10-ml blood sample was drawn for genotypic assay. Debrisoquine and 4-hydroxydebrisoquine were determined in 8-h urine samples. Blood samples were analysed for the presence of mutations in the CYP2D6 gene, by using polymerase chain reaction (PCR) specific for CYP2D6*3 and CYP2D6*4 alleles. RESULTS: The metabolic ratio of debrisoquine to 4-hydroxydebrisoquine ranged from 0.01 to 86.98 in healthy subjects and from 0.02 to 96 in SLE patients. We observed the poor metabolizer(PM) debrisoquine phenotype in three of 39 patients with idiopathic SLE (7.6%) and five of 159 healthy subjects (3.1%). There was no significant difference in the frequency of PM phenotypes between idiopathic SLE and healthy subjects (Fisher's exact test, P = 0.19). No significant difference in the distribution of overall genotypes and allele frequencies were observed between the two groups. No significant relationships were found between specific clinical features and the overall genotype. CONCLUSION: The results of this study confirm that CYP2D6 activity is not impaired in SLE and that there is no association between SLE and phenotypic CYP2D6 status. The results also showed that there was no difference in the frequency of CYP2D6A and CYP2D6B alleles between controls and patients with SLE.

Adult↗

PubMed1999

Human aqueous and vitreous humour levels of ciprofloxacin following oral and topical administration.

PURPOSE: To assess aqueous and vitreous humour ciprofloxacin concentrations following oral and topical administration of ciprofloxacin in patients with non-inflamed cornea and an intact crystalline lens, and to compare the concentrations of the drug given by either route. METHODS: In this prospective study, 34 patients undergoing pars plana vitrectomy for various ocular pathologies were divided into two groups. Eighteen patients received 2 drops of 0.3% ophthalmic solution of ciprofloxacin every 30 min for 3 h and then every 60 min for the next 3 h, and 16 patients received a single oral dose of 1000 mg ciprofloxacin 6 h before surgery. The aqueous and vitreous humour samples were simultaneously harvested after oral or topical administration during pars plana vitrectomy to assess penetration of the drug. These samples were assayed for ciprofloxacin concentrations by a method described previously by us using high-performance liquid chromatography. RESULTS: The aqueous and vitreous humour levels of ciprofloxacin were 0.59 +/- 0.06 microgram/ml (mean +/- SEM) and 0.64 +/- 0.06 microgram/ml after oral and 0.44 +/- 0.07 microgram/ml and 0.22 +/- 0.04 microgram/ml after topical ciprofloxacin administration, respectively. Aqueous humour levels were not statistically significantly different following oral and topical administration (p = 0.069). However, the vitreous level of the drug after oral administration was significantly higher than that after topical administration (p < 0.001). CONCLUSION: Ocular bioavailability of ciprofloxacin in aqueous humour following oral and topical administration is found to be similar when the drug was applied as described above. Penetration of ciprofloxacin into vitreous humour is less than that into aqueous humour after topical administration.

Administration, Oral↗

PubMed1999

Aqueous humour levels of topically applied ciprofloxacin and ofloxacin in the same subjects.

PURPOSE: To evaluate aqueous humour levels of topical 0.3% ciprofloxacin and 0.3% ofloxacin in the same subjects. METHODS: Thirty-two bilateral cataractous patients received topical 0.3% ciprofloxacin in one eye and 0.3% ofloxacin in the other eye before each cataract extraction. Eyedrops were repetitively instilled for 6 h. Aqueous humour samples were collected and assayed for drug concentrations by a method described originally by us using high-performance liquid chromatography. RESULTS: Mean aqueous ciprofloxacin and ofloxacin levels were 0.33 +/- 0.04 microgram/ml (mean +/- SEM) and 1.34 +/- 0.14 micrograms/ml respectively (p < 0.0001). CONCLUSION: Ofloxacin level in the aqueous humour is 4 times higher than that of ciprofloxacin in the same subjects.

Administration, Topical↗

PubMed1999

Low frequency of defective alleles of cytochrome P450 enzymes 2C19 and 2D6 in the Turkish population.

BACKGROUND AND OBJECTIVES: The genetically polymorphic cytochrome P450 enzymes 2Cl9 (CYP2Cl9) and 2D6 (CYP2D6) contribute to the metabolism of about 30% of all drugs. For analysis of the ethnic-related differences in drug disposition and as a preparation for routine genotyping, we examined CYP2C19 and CYP2D6 mutations in a large Turkish population. METHODS: CYP2C19 and CYP2D6 alleles were determined with use of genomic deoxyribonucleic acid from 404 unrelated Turkish individuals. CYP2C19 alleles *1 to *5 and CYP2D6 alleles *1 to *12, and *14, *15, and *17 were measured by polymerase chain reaction-restriction fragment length polymorphism assays. RESULTS: From 404 subjects genotyped for CYP2C19, allele frequencies of CYP2C19*1 (wt), CYP2C19*2 (ml), and CYP2C19*3 (m2) were 0.88, 0.12, and 0.004, respectively; mutations m3 and m4 were not found. Four individuals (1.0%) were predicted to be poor metabolizers (CYP2C19*2/*2), a significantly lower frequency compared to Middle European populations. Among 404 subjects genotyped for CYP2D6, most frequent alleles were CYP2D6*1 (allele frequency 0.37), *2 (0.35), *4 (0.11), *10 (0.06), duplications *1x2, *2x2, or *4x2 (0.06), *5 (0.01), and *17(0.01). Overall, six subjects (1.49%) were predicted to be CYP2D6 poor metabolizers, and 35 subjects (8.66%) were predicted to be ultrarapid metabolizers as a result of CYP2D6 gene duplications. CONCLUSION: Obviously, within Europe there is a north-south gradient, with decreasing frequency of poor metabolizers of CYP2C19 and CYP2D6 to the south and a corresponding increase of ultrarapid metabolizers of CYP2D6. As in other white groups, only CYP2C19*2 plays a relevant role for the CYP2C19 poor metabolizer phenotype. The mutational spectrum of CYP2D6 indicated partial ethnic relationships to Asian and African populations.

Adult↗

PubMed1999

The effect of long-term use and inflammation on the ocular penetration of topical ofloxacin.

PURPOSE: To study the penetration of ofloxacin into the aqueous and vitreous humors after long-term topical administration and to investigate the effects of inflammation on drug penetration in rabbits. METHODS: A standardized model of intraocular infection after penetrating injury was achieved in the right eyes of 16 rabbits. The animals were randomly and equally divided into two groups. The intact left eyes of the groups were maintained as the control. Ofloxacin eyedrops (0.3%) were instilled into all eyes at a frequency of 2 drops every hour for 7 hours in the first group and for 14 hours in the second group. Half an hour after the last drop, samples of the aqueous and vitreous humors were taken and ofloxacin concentrations were measured by using HPLC. RESULTS: The mean aqueous humor concentrations of ofloxacin in control eyes after 7 and 14 hours of instillation were: 1.45 +/- 0.93 microg/ml and 2.48 +/- 0.33 microg/ml, respectively; those in infected eyes 2.35 +/- 1. 84 microg/ml and 3.49 +/- 1.47 microg/ml, respectively. However the differences among the groups were not significant (p > 0.05). The vitreous ofloxacin concentrations in the control eyes were similar after 7 and 14 hours of instillation (0.23 +/- 0.14 microg/ml, 0.27 +/- 0.10 microg/ml, respectively). In infected eyes, the mean vitreous ofloxacin concentration after 14 hour of instillation was significantly higher than that in control eyes (p < 0.05; 0.4 +/- 0. 09 microg/ml, 0.29 +/- 0.11 microg/ml, respectively). The mean vitreous ofloxacin concentration in infected eyes after 14 hours instillation was not significantly higher than that after 7 hours instillation. CONCLUSIONS: Topical ofloxacin instillation for 7 or 14 hours yields aqueous concentrations above the MIC(90) for common ocular pathogens. Prolonged application and the presence of inflammation increased the penetration of ofloxacin into the vitreous humor.

Administration, Topical↗

PubMed1999

Effects of trauma and infection on ciprofloxacin levels in the vitreous cavity.

OBJECTIVE: This study was designed to determine the effects of trauma and infection on vitreous ciprofloxacin levels after intravitreal injection of ciprofloxacin in rabbits. METHODS: A penetrating injury was made in the right eyes of 24 rabbits. In the eyes of half of the traumatized animals, a standardized intraocular infection was induced by intravitreal injection of a suspension of Staphylococcus aureus. The intact left eyes of the traumatized group were maintained as controls. Ciprofloxacin (200 microg/0.1 mL) was injected into the midvitreous cavity of both eyes in all animals and samples were obtained at 2, 8, 24, and 48 hours after injection. Drug concentrations were measured using high-pressure liquid chromatography analysis. RESULTS: At the second hour, the mean vitreous concentration of ciprofloxacin in the traumatized eyes was lower than that in control eyes (P<0.05). The mean ciprofloxacin concentrations were significantly higher (P<0.05) in the traumatized-infected eyes than were those in control or traumatized eyes at 24 and 48 hours. The elimination half-life of ciprofloxacin in control and traumatized eyes was 6.02 hours and 5.02 hours, respectively, and infection prolonged the half-life to 15.06 hours. Vitreous levels of ciprofloxacin were above the minimum inhibitory concentration (MIC90) for most of the common microorganisms causing endophthalmitis in all groups at 2 and 8 hours, but also at 24 and 48 hours in traumatized-infected eyes. CONCLUSION: Infection appears to decrease the clearance of ciprofloxacin. Therapeutic drug levels in traumatized-infected eyes were maintained up to 48 hours. Assuming that the animal model used may have a predictive value for the drug elimination in traumatized-infected human eyes, we suggest that local administration of ciprofloxacin every 2 days may be relevant from the therapeutic perspective.

Animals↗

PubMed1999

Penetration of topical and oral ciprofloxacin into the aqueous and vitreous humor in inflamed eyes.

PURPOSE: To assess the aqueous and vitreous penetration of ciprofloxacin after topical and combined topical and oral administration and investigate the effects of inflammation on drug penetration. METHODS: A standardized penetrating injury was made in the right eyes of 16 rabbits. Intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in these eyes. The animals were divided into two groups according to treatment methodology: topical and topical-oral. The intact left eyes of the animals were maintained as controls. In the topical treatment group, two drops of ciprofloxacin 0.3% were instilled to both eyes every 30 minutes for 4 hours. In the topical-oral treatment group, animals were given two oral 40 mg/kg doses of ciprofloxacin at 12-hour intervals. After the last oral dose, the protocol of the topical group was applied to these eyes. Half an hour after the last drop, 100-microL samples were taken from aqueous and vitreous humor of all eyes. Drug concentrations were measured using high-pressure liquid chromatography. RESULTS: Mean aqueous levels of ciprofloxacin in control eyes were 2.31 microg/mL (range, 1.02-6.27 microg/mL) in the topical group and 5.88 microg/mL (1.52-17.81) in the topical-oral group. Mean aqueous levels in inflamed eyes were 7.36 microg/mL (2.34-17.15) in the topical group and 14.43 microg/mL (2.18-18.66) in the topical-oral group. Mean vitreous levels in control eyes were 0.77 microg/mL (0.09-1.93) in the topical group and 1.01 microg/mL (0.49-1.57) in the topical-oral group. Mean vitreous levels in inflamed eyes were 0.95 microg/mL (0.18-1.27) in the topical group and 1.98 microg/mL (0.51-3.34) in the topical-oral group. There was no significant difference among the groups (P > 0.05). Mean aqueous levels in all eyes and mean vitreous levels in the combined topical and oral group of inflamed eyes were above the 90% minimum inhibitory concentration for most of the common microorganisms causing endophthalmitis. CONCLUSION: There is an increase in both aqueous and vitreous humor concentrations with inflammation and with oral and topical administrations, as opposed to topical only, of ciprofloxacin. Using oral as well as topical treatment may be a beneficial method of antibiotic prophylaxis in ocular trauma once a patient has received intravenous or intravitreal therapy.

Administration, Oral↗