Absorption Of Gentamicin Research Articles

Measurement of plasma gentamicin concentrations postchemical ciliary body ablation in dogs with chronic glaucoma.

To investigate the absorption of gentamicin into the plasma after an intravitreal injection in dogs and to report the success rate of this procedure in lowering the intraocular pressure. Twenty-four client-owned dogs with chronic, end-stage glaucoma. Dogs received a unilateral (22) or bilateral (2) intravitreal injection of 25-40mg of gentamicin (mean±SD dose 2.57±1.65mg/kg and range 0.61-7.50mg/kg) and 1mg of dexamethasone per eye. Blood samples were collected at various time points following the intravitreal injection. Plasma concentrations of gentamicin were determined by liquid chromatography and mass spectrometry. The total plasma concentration of gentamicin ranged from 0.21 to 9.71μg/mL (mean±SD 2.15±2.03). The mean gentamicin CMAX was 2.29μg/mL at 2.54h with a terminal half-life of 9.8h. The success rate of the chemical ablation procedure was 86.4% (19/22 eyes) in dogs that had at least 1month of follow-up. Intravitreal injection of gentamicin in eyes with chronic glaucoma resulted in detectable plasma levels in dogs and was successful in lowering the intraocular pressure in 86.4% of the eyes after the first procedure.

Pharmacokinetics of Intraperitoneal Gentamicin in Peritoneal Dialysis Patients with Peritonitis (GIPD Study)

Peritonitis is a major infectious complication in peritoneal dialysis patients, and intraperitoneal antibiotic administration is preferred to ensure maximal antibiotic concentrations at the site of infection. This study aimed to describe the plasma and infection site pharmacokinetics of intraperitoneal gentamicin in patients with peritonitis. This prospective pharmacokinetic study of intraperitoneal gentamicin was conducted in peritoneal dialysis patients presenting to hospital with clinically defined signs and symptoms of peritonitis. Twenty-four patients were administered a 0.6-mg/kg dose of intraperitoneal gentamicin, which was allowed to dwell for 6 hours. Serial blood and dialysate samples were collected for 24 hours after the first dose. Gentamicin concentrations in plasma and dialysate were measured using a validated assay. The median percentage of the dose absorbed into the systemic circulation was 76% (interquartile range=69%-82%) and significantly different between patients with low average, high average, and high peritoneal membrane transporter status (P=0.03). The calculated pharmacokinetic parameters were plasma terminal elimination half-life of 24.7 (20.4-29.9) hours, terminal volume of distribution of 0.30 (0.20-0.36) L/kg, observed peak plasma concentration of 3.1 (2.4-3.4) mg/L, and observed trough plasma concentration of 1.9 (1.4-2.2) mg/L. The peak gentamicin concentration in dialysate was at least eight times the minimum inhibitory concentration of the likely pathogens. The high systemic absorption of gentamicin in patients with peritonitis and prolonged plasma elimination half-life may lead to drug accumulation in the systemic circulation, increasing the risk of toxicity.

The Prospects of Carrying and Releasing Drugs Via Biodegradable Magnesium Foam

AbstractPowder metallurgy technology was used to produce magnesium foams in order to evaluate their ability to perform as a solid biodegradable platform for drug delivery. The amount and delivery time of the released drug (gentamicin) was controlled by the level of space‐holding particles (spacer) that was mixed with the magnesium powder prior to the sintering process. Metallurgical examination of the magnesium foams was carried out using optical and scanning electron microscopy (SEM) and X‐ray diffraction analysis. Microtomography CT analysis was used to evaluate the structural characteristics of the magnesium foams and their internal interconnected porosity configuration. The corrosion behavior of the magnesium foams was evaluated by immersion test in a simulated physiological environment (PBS solution). The absorption of gentamicin was obtained by immersing magnesium foams in concentrated gentamicin solutions within a vacuum chamber, followed by water evaporation. The detection of gentamicin in PBS solution was carried out using a Fluorescence Polarimetry analyzer. The results show that the release profile of gentamicin from magnesium foam with 10 and 25% spacer in PBS solution was in accord with common dissolution kinetics of an active ingredient from polymeric drug delivery systems.

A Comparison Between The Pharmacokinetics Of Gentamicin And Its Mixture With Calcium In Rabbits

Pharamcokinetic studies were performed for gentamicin sulphate at single dose of 5 mg/kg compared with formullae of same dose of gentamicin with calcium gluconate at a dose of 7.5 mg/kg injected i.v. and i.m. to four groups of 5 rabbits. The results of i.v. injection showed elimination of first order two compartment model with lower plasma gentamicin concentration, lower inhibition bacterial period and increase of gentamicin clearance in mixture group may be due to its competition with calcium for albumin which increase the free drug available for excretion and distribution while after i.m. injection absorption of gentamicin from formullae was lower but its plasma elimination (B) was slower with nearly same inhibition bacterial period as in gentamicin dosed group. These results explain kinetically why calcium lower gentamicin toxic side effect after i.m. and i.v. injection.

Design, synthesis, and evaluation of a liposaccharide drug delivery agent: application to the gastrointestinal absorption of gentamicin.

The design, synthesis, and evaluation of a liposaccharide (11) for use as an agent to enhance the gastrointestinal absorption of charged, hydrophilic drugs with poor membrane permeability is reported. 11 was designed to possess both surfactant and ion-pairing properties and was conveniently synthesized from d-glucuronic acid (2) and N-Boc-lipoamino acid (5) precursors in eight steps in good yield. Isothermal titration microcalorimetry was used to determine the critical micelle concentration of 11 (in PBS) to be 2.09 +/- 0.01 mM with an enthalpy of demicellization of 4.91 +/- 0.11 kJ/mol. The ability of 11 to enhance the gastrointestinal absorption of the aminoglycoside antibiotic gentamicin (1), a hydrophilic polycation with negligible oral bioavailability, was assessed in vivo using rats. Rats dosed orally with a mixture of 11 (100 mg/kg) and 1 (60 mg/kg) had a statistically significant (P < or = 0.034) increase in Cmax, AUC120, and percent absolute bioavailability (F) compared to control 1 (60 mg/kg) alone. The highest bioavailability (F = 9.1 +/- 2.0%) was achieved by dosing with the mixture 11 (100 mg/kg) and 1 (15 mg/kg). This represents a 6-fold increase in bioavailability compared to the control (F = 1.4 +/- 0.3%). These results suggest that the molar ratio of 1:11 may be critical in optimizing the delivery system, a finding ascribed in part to the ion-pairing properties of 11. The effect of 11 on the gastrointestinal mucosa was assessed using light microscopy to examine tissue samples from rats used in the pharmacokinetic study. No morphological changes were found in either the esophagi or duodena of the rats examined. One rat dosed with 11 (100 mg/kg) and 1 (60 mg/kg) exhibited slight gastric erosion, which could be attributed to 11.

Round window gentamicin absorption: an in vivo human model.

Using a novel human labyrinthine sampling model, in vivo gentamicin absorption through the round window can be measured. A prospective study. Gentamicin was delivered either transtympanically (preoperative) or through a facial recess approach (intraoperative). The lateral semicircular canal and vestibule were opened, and by means of a microsyringe, labyrinthine fluid was aspirated. A sample of serum was also drawn. In all patients cerebrospinal fluid was also drawn. The samples were analyzed using a standard chemistry analyzer. Intratympanic gentamicin diffused through the round window membrane and achieved concentrations in the labyrinthine fluid ranging from 0 to 16 mg/L. Intratympanic gentamicin was absorbed into the systemic circulation in 4 of 11 patients with serum levels ranging from 0.3 to 0.4 mg/L. No gentamicin was detected in the cerebrospinal fluid. Intratympanic gentamicin diffuses rapidly through the round window membrane and achieves significant levels in the inner ear. Thus, this new model can be used to assess round window permeability to clinically relevant medications such as steroids and ototopical antibiotics.

A novel emulsifier, Labrasol, enhances gastrointestinal absorption of gentamicin

Gentamicin (GM) is an important aminoglycoside antibiotic for the treatment of infections caused by a wide spectrum of aerobic gram-negative bacilli and gram-positive cocci. As a class, the aminoglycosides are poorly absorbed from the gastrointestinal (GI) tract and are commonly used as injectable and topical preparations. This study was aimed at finding the effect of a novel emulsifier, Labrasol, on the absorption of GM from the GI tract of rats. GM formulations were prepared, either as saline solution or as Labrasol microemulsions, and were administrated to rat small intestine and colon. Plasma GM levels following intestinal application were compared to those obtained with intravenous (i.v.) administration. A 5 mg/kg dose of GM preparation containing Labrasol, 1 ml/kg, administrated into colon resulted in the mean AUC of 21.179±1.374 μg×h/ml, compared to 7.813±0.105 μg×h /ml obtained with i.v. administration of GM, 1 mg/kg. The absolute bioavailability (BA) of the Labrasol preparation was 54.2 %. Labrasol facilitates the transmucosal delivery of GM from rat colon by forming microemulsions, and the BA obtained with Labrasol microemulsion was higher than with other surfactants (8.4 % for Tween 80 and 3.4 % for Transcutol P). Additionally, in vitro permeation studies demonstrated that Labrasol also inhibited the intestinal secretory transport. The effect of Labrasol is ascribed to both (1) enhanced GM absorption from the GI lumen into the systemic circulation and (2) inhibition of efflux of GM from the enterocytes to the GI lumen.

Systemic absorption of gentamicin in the management of active mucosal chronic otitis media.

A prospective study was performed on patients with active mucosal chronic otitis media who were being treated with the gentamicin-containing preparation Gentisone HC. In 27 patients plasma gentamicin levels were measured. Detectable levels were found in 7/27 (26%). Pre- and post-treatment audiometry was performed on 16 patients. There was no statistically significant difference in the change of the mean bone conduction thresholds as a result of treatment, between the treatment and control ears (P = 0.07, Wilcoxon signed Ranks Test at 95% C.I.). We conclude that there is evidence of systemic absorption of gentamicin that would ultimately be absorbed into the perilymph. Gentamicin is known to be ototoxic affecting the vestibular system in lower doses and the cochlea in high doses, hence audiometric assessment is not an appropriate screen for ototoxicity when using topical gentamicin-containing drops. Alternative topical preparations should be further investigated.

Kinetics of gentamicin uptake in the inner ear of Chinchilla langier after middle-ear administration in a sustained-release vehicle

The search for a safe, effective treatment for the vertigo associated with Meniere’s disease has long been an important topic in otolaryngology. In recent years many groups have begun using intratympanic gentamicin to treat this vertigo. Although reported cure rates are as high as 90%, many questions remain regarding this type of treatment. Current limitations are the necessity for repeated treatments and a lack of clear dosing guidelines. In addition, the gentamicin must be delivered in a manner that allows maximal vestibulotoxic effect without injury to hearing. Until investigators can control the exact amount of medicine that is placed in the ear and have an understanding of the kinetics of gentamicin absorption, adequate dosing guidelines will be difficult to establish, and therapy will continue to rely on empiric data. We describe the use of a fibrin-based sustained-release vehicle, impregnated with gentamicin, injected into the middle ear of chinchillas. This allows for a prolonged effect without repeated dosing. Using this model, we studied the absorption kinetics of gentamicin at time points ranging from 8 hours to 1 week after injection. We used our findings to create a kinetics curve of gentamicin absorption. We discuss the shape and characteristics of this kinetics curve and examine the effects of the fibrin-based sustained-release vehicle and gentamicin on the middle ear. We noted no absorption in the contralateral (untreated ear) or blood. Through better understanding of the actions of gentamicin in this animal model, we hope to facilitate safer use of intratympanic medicines in our patient population and initiate programs for the use of this sustained-release vehicle in human beings. (Otolaryngol Head Neck Surg 1998;119:427-31.)

Systemic absorption of gentamicin following intramammary administration to cows with mastitis [correction of mastititis

Systemic absorption of gentamicin following intramammary administration to cows with mastitis [correction of mastititis

Systemic absorption of gentamicin in penile prosthesis operations.

Irrigation with antibiotic solutions is frequently used in penile prosthesis surgery to avoid infection. We carried out a prospective study to determine the degree of absorption of gentamicin after intracavernous irrigation in 10 patients who underwent penile implantation surgery. All obtained values were below the toxic level of 10 micrograms/ml and decreased gradually within a few hours. We concluded that highly concentrated gentamicin solutions could be used with safety for intracavernous irrigation.

Duration of absorption-enhancing effect of sodium octanoate, sodium hexanoate or glycery-1-monooctanoate on rectal absorption of gentamicin in rabbits.

The duration of the absorption-enhancing effect of sodium octanoate (C8), sodium hexanoate (C6) and glyceryl-l-monooctanoate (MO) on the rectal absorption of gentamicin (GM) using the hollow-type suppository was investigated in rabbits. To evaluate the duration of the absorption-enhancing effect by pretreatment (treatment of absorption enhancer before GM administration), suppository I containing each absorption enhancer in the cavity was administered into the rectum. Then suppository II containing GM in the cavity was administered at predetermined times (0.33, 2, 6 and 24 h) after the administration of suppository I. Plasma GM levels obtained by the pretreatment with absorption enhancer were compared with those obtained by the simultaneous administration of GM with absorption enhancer. The AUC and Cmax of GM significantly decreased with the pretreatment of C8 (6 and 24 h), C6 (2 and 6 h) or MO (6 and 24 h) before rectal GM administration, as compared with the simultaneous administration of GM with C8, C6 or MO. A marked decrease in the absorption-enhancing effect of C8, C6 and MO on rectal GM absorption was observed by the prolongation of the period between the pretreatment of each absorption enhancer and GM administration. The duration of the absorption-enhancing effect of C6 was shorter than that of C8, whereas this duration of MO was similar to that of C8. The effect of these absorption enhancers disappeared 24 h after the pretreatment. These results suggested that the lowering of the membrane transport barrier function recovered about one day after the administration of C8 or MO.

Vaginal administration of gentamicin to rats. Pharmaceutical and morphological studies using absorption enhancers

The vaginal absorption of gentamicin in ovariectomized rats was markedly increased by the coadministration of absorption enhancers. By comparison of the AUCs of the serum concentrations of gentamicin with time profiles, the enhancers investigated could be ranked in terms of efficacy; 1% palmitoylcarnitine 0.5% lysophosphatidylcholine 1% laureth-9 10% citric acid. The acute effects of solutions of gentamicin and enhancers on the morphology of the vaginal epithelium were quantitated. All enhancers significantly reduced epithelial thickness with laureth-9 and lysophosphatidylcholine causing complete desquamation of approximately 50% of the areas assessed. On the basis of these data, it was possible to rank the severity of the interaction of the drug and enhancer solutions with the vaginal lining; 0.5% lysophosphatidylcholine = 1% laureth-9 1% palmitoylcarnitin 10% citric acid.

Gentamicin solution for mediastinal irrigation: Systemic absorption, bactericidal activity, and toxicity

Local irrigation with gentamicin sulfate represents a possible substitute for neomycin sulfate, used for many years but now no longer available for use as an irrigation fluid. In this investigation, mediastinal irrigation with gentamicin was used in 12 patients who had experienced problems after a heart operation. The regimen employed for mediastinal irrigation with gentamicin was equipotent with that using neomycin. We sought to determine the degree of and risk of either inadequate or toxic blood levels that might follow gentamicin absorption. Irrigation periods were short, ranging from one to four days and determined by measurements of plasma gentamicin concentration using radioimmunoassay evaluation. Systemic gentamicin absorption occurred in all patients. Toxic levels of higher than 8.0 μg/mL occurred and were size related, ie, correlated with smaller body weight and surface area, and sex related, ie, female sex. Larger-sized patients often had inadequate levels. Despite the potential risk from toxic blood levels, major increases in serum creatinine levels were not seen. These findings suggest that monitoring of plasma gentamicin levels during mediastinal irrigation with gentamicin is mandatory to avoid both inadequate treatment and toxicity.

Enhancing effect of glyceryl-1-monooctanoate on the rectal absorption of gentamicin from hollow-type suppositories in rabbits.

A hollow-type suppository containing gentamicin (GM) in its cavity was prepared using Witepsol H-15 (H-15) mixed with glyceryl-1-monooctanoate (MO) or MO alone in the body of the suppository (type I) and a suppository (type II) containing GM and MO in the cavity was constructed using H-15 in the body of the suppository. Without MO, GM (60 mg) was not absorbed (plasma GM levels less than 1 microgram/ml). However, the absorption of GM from the rectum of rabbits was enhanced by coadministered MO in types I and II. Even when the amount of GM was decreased to 6 mg (1/10), GM was observed in the plasma (Cmax, 3.5 +/- 0.3 micrograms/ml) after administration of the suppository made from MO mixed with H-15. The enhancing effect of MO on the rectal absorption of GM could not be further increased by incorporating an amount of MO larger than approximately 300 mg into the suppository. This study demonstrates that MO can be used in the two types of hollow suppositories as an effective enhancing agent of rectal absorption of poorly absorbed drugs such as GM.

Gentamicin bioavailability and single-dose pharmacokinetics in spinal cord injury.

The rate and completeness of absorption of gentamicin from muscle (healthy and paralyzed) and gentamicin disposition kinetics following a single intravenous infusion were studied in nonobese, healthy male volunteers with functionally complete, chronic (greater than one year duration) spinal cord injury (SCI) and in able-bodied controls. Pharmacokinetic parameters were derived using compartmental and model-independent analyses. The absolute bioavailability of gentamicin was complete and did not differ from control values using both model-independent (LAGRAN) and model-dependent (ADAPT) analyses. The rate of gentamicin absorption in patients with SCI was, however, significantly slower, with a mean absorption time of 2.55 h compared with 0.96 h in able-bodied controls (p less than or equal to 0.05). Mean volume of distribution steady-state (Vssd) of gentamicin was demonstrated to be 33-47 percent greater in spinal cord injury than in controls (p less than 0.05). We conclude that the absorption of gentamicin from paralyzed muscle is significantly impaired, and in conjunction with an increase in Vssd results in delayed, decreased peak serum levels in patients with SCI.

Sustained release of liposome-encapsulated gentamicin and fate of phospholipid following intramuscular injection in mice

Gentamicin sulfate was encapsulated in liposomes comprised of either egg or soy-sourced phosphatides, administered via intramuscular injection to ICR mice, and measured in plasma over twenty-four hours. 125I-labeled liposomes of the same compositions were administered via intramuscular injection to ICR mice and the retention, tissue distribution, and elimination of the radiolabel assessed over six days. There was a seven-fold difference in the systemic gentamicin absorption rate constants, and a 20% difference in retention of radiolabeled lipid at the injection site between egg and soy-sourced liposomes. The results suggest that differences in the percentage of unsaturated fatty acids, known previously to affect the fluidity of liposomal membranes, will influence systemic drug input from liposomal dosage forms.

Bile salts and intranasal drug absorption

The nasal route has been proven to be very effective for drug absorption. Bioavailability of intranasally administered drugs depends on the structure of the drug and can be as high as 100%. The absorption of drugs with a lower bioavailability can be improved with the aid of absorption promotors such as some surfactants, e.g. bile salts. The intranasal absorption of gentamicin, as a model drug, was studied in rabbits with six different bile salts as absorption promotors (cholate, taurocholate, glycocholate, deoxycholate, taurodeoxycholate and glycodeoxycholate). Without a surfactant, gentamicin is not absorbed by the nasal mucosa. The serum concentrations of gentamicin after intranasal administration were compared with those obtained after an intravenous injection. Concentrations were measured with EMIT. The bioavailability of the intranasal gentamicin in rabbits was related to the hydrophobicity and the pK a's of the bile salts. Furthermore the effects on ciliated epithelium of the six bile salts, used in the absorption experiment, were studied in an in vitro model. Ciliary activity was studied with a photo-electric method. Bioavailability increased with the increase of the hydrophobicity of the trihydroxy bile salts (cholate, taurocholate and glycocholate). Sodium cholate and sodium taurodeoxycholate were the most active absorption promotors (F = 41 ± 16%, respectively, 34 ± 13%). The dihydroxy bile salts (deoxycholate, taurodeoxycholate and glycodeoxycholate) showed a decreasing activity in the promotion of gentamicin absorption as the hydrophobicity increases. Depending on the pH/pK a relation, increasing hydrophobicity results in lower solubility and therefore decreasing activity. Ciliotoxicity of the bile salts increased with increasing hydrophobicity. Dihydroxy bile salts are more toxic than trihydroxy bile salts. At the used concentrations ciliary beat arrested within 30 min. Deoxycholate is extremely ciliotoxic, ciliary arrest occurred within 1 min at a concentration of 5 mmol/l.

Alimentary absorption of gentamicin in preterm infants.

Fifty-two preterm neonates receiving oral gentamicin from birth, as prophylaxis against necrotizing enterocolitis (NEC), had serum gentamicin levels measured on the second day of life (52 infants) and on the seventh to tenth days (43 infants). The serum gentamicin concentrations on the second day were 0.5 microgram/ml or less in 21 percent, 0.6 to 1.0 microgram/ml in 15 percent, 1.1 to 2 micrograms/ml in 34 percent, 2.1 to 5 micrograms/ml in 25 percent, and 5 to 7.1 micrograms/ml in 4 percent of the infants. Paired serum gentamicin levels were significantly lower (p less than 0.001) on the seventh to tenth day as compared to the second day. We conclude that preterm infants in the first few days of life absorb orally administered gentamicin. Concomitant use of systemic gentamicin under such circumstances may potentially lead to toxic serum gentamicin concentration.

Gentamicin absorption during prophylactic use for necrotizing enterocolitis.

Gentamicin absorption was measured after oral administration in 18 neonates treated prophylactically in an attempt to decrease the incidence of necrotizing enterocolitis. Patients were given 10 mg/kg/day in four divided doses via nasogastric tube for a total of 10 days. Levels were assayed using the Emit system. Serum levels ranged between 0 and 2.2 micrograms/ml. Mean levels over 10 days were 0.42 +/- (SD) 0.47 micrograms/ml and did not vary significantly from day to day. From these data we conclude that enterally administered gentamicin is not absorbed to a degree that would result in toxic or even therapeutic serum concentrations.