Intravitreal delivery of ciprofloxacin.

The objective of this work was to evaluate various methods of sustained delivery to achieve therapeutic intravitreal levels of ciprofloxacin as a potential therapy for endophthalmitis. Two types of intravitreal bioerodible sustained release devices of ciprofloxacin were evaluated in vitro. The most promising device was evaluated in rabbits and results compared with subconjunctival injections of a ciprofloxacin suspension. Subconjunctival injections failed to deliver therapeutic concentrations of ciprofloxacin into either the aqueous or vitreous. In vivo evaluation of the intravitreal device consistently delivered ciprofloxacin at levels above 1 ug/ml for up to four weeks. No retinal activity was noted by clinical examination or by electroretinogram. Intravitreal implantation of bioerodible ciprofloxacin devices can maintain vitreous concentrations above 1 ug/ml, more than the MIC90 of most organisms associated with endophthalmitis. Implantation of these devices appears to be well tolerated and may represent a viable treatment for this disease. Further studies in endophthalmitis models are needed to evaluate device efficacy.

Sustained release intravitreal dexamethasone.

Sustained intravitreal levels of dexamethasone may be useful in the treatment of proliferative vitreoretinopathy (PVR). The preparation and evaluation of an implantable system for intravitreal sustained release of dexamethasone is described. Pellets of dexamethasone were coated in biocompatible, nonerodible polymers and the release rate tested in vitro. Devices were then implanted in the rabbit vitreous and the in vivo release rate and corresponding steady state vitreous concentration determined. Toxicity was also evaluated by histopathology and electrographic examination. Devices released dexamethasone at approximately 1 ug/hr in vitro and 1.5 ug/hr in vivo. When implanted into the vitreous intravitreal concentrations of approximately 2.5 +/- 1.2 ug/hr were maintained for over 3 months. Devices were well tolerated with no evidence of inflammation or retinal abnormalities.

An evaluation of four multifocal contact lenses in young monocular aphakic patients.

To evaluate the efficacy of multifocal contact lenses in the correction of presbyopic symptoms we fit six young monocular aphakic patients with four different bifocal contact lenses (ACC, Tangent Streak, VFL, and Constavu). Each patient had 20/20 uncorrected vision and normal accommodation in the other eye. We evaluated both subjective and objective parameters of comfort and vision for all four lenses. We found no significant overall performance advantage among the four lenses based on comfort, visual satisfaction, visual acuity, contrast sensitivity, or wear-related corneal complications.

Bioavailability of single and multiple doses of enteric-coated mesalamine and sulphasalazine.

The bioavailibity of mesalamine from enteric-coated mesalamine and sulphasalazine was determined following a single dose and at steady state in healthy subjects in crossover studies. Plasma concentrations and urinary excretion of mesalamine and its major metabolite, N-acetyl-5-aminosalicylic acid, were measured. After a single dose of enteric-coated mesalamine, about 10 h elapsed before the onset of measurable plasma drug concentrations, probably representing gastro-intestinal transit prior to drug release near the ileocaecal junction. The elimination kinetics were similar for a single oral dose and steady state using enteric-coated mesalamine, but after both single and multiple administration of enteric-coated mesalamine only about 20% of the mesalamine given was absorbed, with about 80% estimated to remain for colon therapeutic activity. It is concluded that, despite different mechanisms of mesalamine release, enteric-coated mesalamine and sulphasalazine produced similar mesalamine absorption.

Between-lot and within-lot comparisons of bioavailability of macrocrystalline nitrofurantoin capsules.

Comparative bioavailability studies should be designed and the resulting data evaluated based on estimates of both intersubject and intrasubject variances in the kinetic parameters for the particular drug products(s) being studied. This report presents the results of two comparative bioavailability studies. In the first study, three production lots of macrocrystalline nitrofurantoin capsules (Macrodantin) were compared in 21 subjects, and in the second study, capsules from one production lot were administered to 21 different subjects on three occasions. Both model-independent kinetic parameters for urinary excretion and a one-compartment model with zero-order absorption were used to evaluate both the rate and the extent of bioavailability. Overall the results showed a very low variance between and within production lots and a relatively large intersubject variance in the rate and extent of absorption.

Acquired Brown's syndrome from blunt orbital trauma.

Blunt trauma to the supero-medial orbit resulted in an isolated Brown's syndrome in two patients. One recovered spontaneously in three weeks; the other had a good outcome after surgery two years post trauma. Recognition of the characteristic motility abnormality and forced duction testing will differentiate this condition from other, more common, motility disorders caused by orbital trauma. Spontaneous resolution may occur but in persistent deviations a superior oblique muscle weakening procedure should be considered.

The pharmacokinetics of nitrofurantoin and its related bioavailability.

Nitrofurantoin is a urinary tract antibacterial agent whose clinical effectiveness depends on the high urinary drug levels encountered during therapeutic drug dosage. Under these conditions, only low blood drug concentrations are usually found. On the basis of urinary nitrofurantoin excretion determined after oral and intravenous drug administration, orally administered nitrofurantoin in a suitable dosage form is well absorbed. In vitro testing does not accurately reflect nitrofurantoin bioavailability, which is affected by formulation differences, drug particle size, and dosage form. Nitrofurantoin is readily absorbed and quickly distributed into most body fluids. It is rapidly excreted in large amounts in bile and urine. With the exception of the active drug secretion in the kidney tubule and biliary drug transport, nitrofurantoin transfer across body membranes occurs by diffusion. Nitrofurantoin has a short elimination half-life in whole blood or plasma. In conjunction with its rapid excretion by the primary routes, there is little evidence for any prolonged binding of nitrofurantoin to either plasma proteins or tissues. The first-order kinetics involved in nitrofurantoin absorption and elimination is most appropriately described by a one-compartment open model. Biliary and urinary excretion of unchanged nitrofurantoin and enzymatic degradation are the primary means of elimination.

Further studies on nitrofurantoin excretion in dog hepatic bile.

1. Results obtained with a dog donor-recipient model indicate that following intravenous administration of nitrofurantoin sodium, nitrofurantoin is subjected to enterohepatic cycling. At least one-third of the nitrofurantoin originally excreted in the donors' bile after a nitrofurantoin dose of 3 mg/kg is reabsorbed intestinally in the recipients within 3 hours.2. After intraduodenal administration of a nitrofurantoin suspension to dogs at doses ranging from 2 to 12 mg/kg, about 10% of the dose is recovered in bile as nitrofurantoin within 6 hours. A hydrocholeretic effect was also observed which correlated with the amount of drug administered. Both biliary drug excretion and the related hydrocholeresis appeared linearly related over the drug dose range.3. The hydrocholeresis observed in dogs within 3 h after intravenously administered nitrofurantoin sodium, equivalent to 3 mg/kg nitrofurantoin, was at least ten times that seen following the intravenous administration of an equimolar dose of dehydrocholic acid given as its sodium salt.

Excretion of nitrofurantoin in dog hepatic bile.

1. After the intravenous administration of nitrofurantoin sodium to dogs at nitrofurantoin doses of 1.5-24.0 mg/kg, a substantial amount of nitrofurantoin is excreted in bile. The bile to blood drug ratios were about 200. A marked hydrocholeretic effect which correlated directly with the amount of nitrofurantoin administered was also observed.2. The excretion of nitrofurantoin in bile and the hydrocholeretic effect were linear with the dose of drug over the range 1.5-12.0 mg/kg. Maximum increases in hepatic bile flows were usually from 5-10 ml/0.5 h, while average control bile flow was 1.6 ml +/- S.D. 0.6/0.5 hours. The lowest dose at which the hydrocholeretic effect was still detectable was 0.09 mg/kg.3. Apparent saturation of the biliary excretion system for nitrofurantoin and the hydrocholeretic mechanism occurred after a dose of 24.0 mg/kg. Saturation of the urinary system for nitrofurantoin excretion was noted after a dose of 6.0 mg/kg.4. Biliary nitrofurantoin recoveries ranged from 16.5% +/- S.D. 4.2 to 22.6% +/- S.D. 4.7 for the 6 h period after doses of 1.5, 3.0, and 6.0 mg/kg. Urinary nitrofurantoin recoveries for the same interval ranged from 24.1% +/- S.D. 6.6 to 36.2% +/- S.D. 8.3.5. In comparison to values obtained in normal dogs, only about one-tenth of the drug excretion in bile and about one-fifth of the hydrocholeretic effect were obtained after intravenous drug administration to dogs with hepatic impairment induced by CCl(4).