Washout effect vs drug interaction.
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Adrenal Cortex Hormones↗
Biomedical subjects
M Barza
Publications and source records attributed to M Barza.
Comparing radioactive and trephine-disk bioassays of dicloxacillin and gentamicin in ocular tissues in vitro.
Trephined disks of tissue (6 mm diameter) from fresh rabbit eyes were immersed overnight in solutions of radioactive carbon (14C)-dicloxacillin or gentamicin, then assayed by one of two methods: agar-diffusion bioassay, using filter-paper disks immersed in known concentrations of antibiotic as standards, or radioactive assay. The bioassay underestimated the concentrations of antibiotic in sclera and iris by 38 to 72%, and slightly overestimated those in the cornea. A corrected bioassay was calculated, based on the differences in fluid mass between tissue specimens and filter-paper disks; this value was within 20% of the radioactive assay in 18 of 24 experiments with dicloxacillin, and in 14 of 24 with gentamicin. There was evidence of pronounced binding of gentamicin to ocular tissues (iris greater than sclera greater than cornea); this appeared to be a saturable and reversible phenomenon. Less marked binding of dicloxacillin to iris and sclera was noted. The results indicated that, depending on the degree of accuracy required, the corrected trephine-disk agar-diffusion bioassay provides a reasonable estimate of the antibiotic content of ocular tissues.
Animals↗
Regional differences in ocular concentration of gentamicin after subconjunctival and retrobulbar injection in the rabbit.
We compared the penetration of radioactive carbon (14C) labeled-gentamicin into ocular tissues and fluids of albino rabbit eyes after subconjunctival (anterior subtenon's) and retrobulbar (posterior subtenon's) injections. In both normal and infected (Staphylococcus aureus endophthalmitis) eyes, higher levels of drug were produced with subconjunctival rather than with retrobullar admininistration in cornea, sclera, choroid and retina (as a unit), and iris; levels in the aqueous and vitreous humors of infected eyes were similar with the two routes of injection. Marked regional variations in the concentrations of gentamicin were noted in cornea, sclera, and choroid-retina after subconjunctival therapy. The pattern of these variations suggests that subconjunctival antibiotic penetrates the eye by direct diffusion. The low levels of drug after retrobulblar injection may be due to systemic absorption through the highly vascular orbital plexus of the rabbit.
Absorption↗
Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 1: tetracyclines.
The mode of action, bacterial resistance, in vitro activity, pharmacology, dosage, adverse reactions, interactions and indications for tetracyclines are reviewed. Suggestions for the selection of a particular tetracycline are provided. It is concluded that there is only one pertinent difference among the tetracyclines, namely, that doxycycline, and probably minocycline, can be given in full dosage and with minimal risk to patients with renal impairment.
Bacteria↗
Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 2: penicillins.
The mechanism of action, resistance, antibacterial spectrum, clinical pharmacology, adverse effects, and therapeutic and prophylactic use of penicillins are reviewed. The choice of a penicillin is discussed. The only indication for the penicillinase-resistant penicillins is the suspected or demonstrated presence of Staphylococcus aureus. There are no important differences in therapeutic effect among oxacillin, cloxacillin, dicloxacillin or flucloxacillin by the oral route, or among oxacillin, dicloxacillin, nafcillin or methicillin parenterally. Ampicillin is especially useful for infections due to Haemophilus influenzae and Escherchia coli and for serious disease due to enterococcus and Listeria monocytogenes. Carbenicillin and ticarcillin exhibit unique activity against gram-negative bacilli (except Klebsiella).
Bacteria↗
Antimicrobial spectrum, pharmacology, and therapeutic use of antibiotics. III. Cephalosporins.
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Bacteria↗
Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 3: cephalosporins.
Various aspects of the cephalosporin antibiotics are reviewed, including mode of action and mechanisms of bacterial resistance, antibacterial activity, clinical pharmacology, adverse reactions, and therapeutic use. There are no important therapeutic differences between the two oral agents, cephalexin and cephradine. For intramuscular injection, cephaloridine has largely been replaced by cefazolin which is equally well tolerated and not as nephrotoxic; further, cefazolin has a relatively long half-life which permits its administration three or four times daily. There are no substantial therapeutic differences among the cephalosporins most commonly used intravenously--cephalothin, cefazolin and cephapirin. However, cefazolin is administered in a lower dosage and somewhat less frequently.
Bacteria↗
Drug therapy reviews: Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics--part 4: aminoglycosides.
The aminoglycoside antibiotics are reviewed with regard to mechanism of action, bacterial resistance, antimicrobial spectrum, combinations with other agents, pharmacology, dosages in patients with normal and impaired renal function, adverse reactions, therapeutic use, prophylatic use and selection. Streptomycin is suggested in the therapy of tuberculosis, brucellosis, tularemia and yersinia infections; several of these require the coadministration of another agent. The choice between streptomycin and gentamicin for combination therapy of enterococcal endocarditis may be simplified by knowledge of the prevalence of high-level streptomycin-resistant strains in the hospital or by use of an in vitro screening test. Neomycin is the agent used orally in the treatment of hepatic encephalopathy. Paromomycin is indicated only for the treatment of amebic infections. The major difference among gentamicin, tobramycin and amikacin lies in the low but increasing prevalence of gram-negative bacilli which are resistant to gentamicin and tobramycin and susceptible to amikacin. In those institutions in which gentamicin-resistant strains are of concern, amikacin is the aminoglycoside of choice in high-risk patients until the infecting bacterium has been determined.
Aminoglycosides↗
Antimicrobial spectrum, pharmacology, and therapeutic use of antibiotics. IV. Aminoglycosides.
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Adult↗
Comparative pharmacokinetics of cefamandole, cephapirin, and cephalothin in healthy subjects and effect of repeated dosing.
Cefamandole nafate, cephapirin, and cephalothin were administered intravenously in crossover fashion to 12 volunteers, in dosages of 2 g every 6 h for 16 doses. Mean peak levels of cefamandole were approximately 50% higher than those of the other agents. The serum concentration curves appeared to decline bi-exponentially, suggesting that a two-compartment model was most applicable for pharmacokinetic analysis; accordingly, the t((1/2)) of cefamandole was significantly longer when the serum peak was omitted from the analysis (0.86 versus 0.73 h, P < 0.05). The half-lives of cephalothin and cephapirin, 0.34 and 0.36 h, respectively, were probably underestimates reflecting the inclusion of distribution-phase values in the calculation. Repeated dosing had no effect on the peak serum levels, half-life, serum clearance, or apparent volume of distribution with one exception: peak serum levels of cephapirin were significantly lower after the sixteenth than after the first dose. Marked variations within a given subject were noted in the half-life and apparent volume of distribution of cefamandole in several instances. Renal clearances of cefamandole exhibited saturation kinetics similar to those of penicillin G.
Cephalosporins↗
Inhibition of antibiotic activity in vitro by synthetic melanin.
Synthetic melanin (100 to 1,000 mug/ml) markedly inhibited the in vitro activity of aminoglycosides and tetracyclines but did not affect the activity of betalactam antibiotics, erythromycin, or clindamycin.
Aminoglycosides↗
Protective effect of cephalothin against gentamincin-induced nephrotoxicity in rats.
The possibility that the nephrotoxicity of gentamicin may be potentiated by the concomitant administration of cephalothin was examined in a rat model. Cephalothin given once daily in dosages up to 800 mg/kg per day for 10 days produced no renal damage. Gentamicin, at 6 to 50 mg/kg per day, caused pathological changes which were dosage related and affected primarily the proximal tubular cells. Administration of the two drugs simultaneously resulted in a significant protective effect of cephalothin against gentamicin-related nephrotoxicity (P < 0.01). When the daily injections of the two agents were separated by an interval of 6 h, the protective effect was lost, and the resultant damage was the same as that due to gentamicin alone. The protective effect of cephalothin was reproduced by the administration of equiosmolar amounts of sulfate (sodium sulfate), suggesting that the phenomenon might be related to the presence of nonresorbable anion in the urine. These studies indicate that, in the rat, cephalothin does not potentiate, but, in fact, may prevent the nephrotoxic effects of gentamicin.
Animals↗
Comparative incidence of phlebitis due to buffered cephalothin, cephapirin, and cefamandole.
Buffered cephalothin, cefamandole, and cephapirin were compared with respect to their tendency to produce phlebitis. Two grams of each agent was administered every 6 h for 4 days to 12 healthy volunteers in a double-blind crossover fashion. Approximately 50% of intravenous sites developed mild (grade 1) phlebitis and 25% developed moderate (grade 2) phlebitis. The frequency of grade 1 inflammation did not differ significantly among the three cephalosporins. The proportion of individuals eventually exhibiting grade 2 phelebitis was highest with cefamandole, lowest with cephalothin (P = 0.07), and intermediate with cephapirin; however, cephapirin required a substantially greater number of doses to produce grade 2 phelebitis than did the other two drugs. These findings, together with the results of other reports, suggest that interpretation of the phlebitogenic potential of these antibiotics must be made with caution.
Adolescent↗
Effect of cephalothin on renal cortical concentrations of gentamicin in rats.
Renal cortical concentrations of gentamicin were significantly lower in rats given this aminoglycoside and cephalothin simultaneously than in animals given gentamicin alone. This effect may be responsible, in part, for the reduction in nephrotoxicity reported previously in animals given the combination of drugs.
Animals↗
Significant reduction in the incidence of phlebitis with buffered versus unbuffered cephalothin.
Cephalothin (1 g every 2 h), buffered cephalothin, and diluent alone (5% dextrose in water) were each administered for 4 days intravenously to 12 volunteers in a double-blind crossover study. The incidence of phlebitis with buffered cephalothin was significantly lower than that with unbuffered drug (P < 0.01) and almost identical to the incidence with diluent alone.
Adult↗
Activity of cefamandole and other cephalosporins against aerobic and anaerobic bacteria.
The activity of cefamandole was comparable to that of cephalothin, cefazolin, and cephaloridine against Staphylococcus aureus, Streptococcus pyogenes, and Diplococcus pneumoniae. In contrast, cefamandole was considerably more active than cephalothin, cefazolin, or cephaloridine against gram-negative facultative bacilli, including Haemophilus influenzae, the most striking disparities being noted with indole-positive Proteus and Enterobacter. Bacteroides fragilis was more susceptible to cefoxitin than to cefamandole or cefazolin (median minimal inhibitory concentration, approximately 8, 32, and 32 mug/ml, respectively); cephalothin exhibited still less activity against this species. The majority of other anaerobes were inhibited by relatively low concentrations of all four cephalosporins. The results indicate a potentially valuable role for cefamandole against facultative gram-negative bacilli, including H. influenzae, but no exceptional activity against anaerobes.
Aerobiosis↗
Pharmacokinetics of the penicillins in man.
The purpose of this article is to review and summarise those aspects of the pharmacokinetic behaviour of the penicillins that may be of particular interest to the clinician. While these antibiotics differ markedly in their acid stability and oral absorption, misleading inferences may be drawn from simple inspection of the maximal serum concentrations produced by a given dose administered orally. A more accurate picture emerges when serum protein binding and intrinsic activity of the drugs are taken into account. All of the penicillins are readily and actively secreted by the renal tubles and most are eliminated, almost completely unchanged, in the urine. The majority are excreted in small quantities in the bile, but this is a major route for elimination of nafcillin from the body. Distribution of the penicillins in 'non-specialised' sites is excellent. In contrast, penetration of the central nevous system and eye are poor, and of the prostate, minimal. Inflammation reduces the barries to penetration of these areas. However, quantitative data related to this phenomenon in man are few. Probenecid actively competes with the 'export' pump of the meninges and renal tubular cells. This results in an increase in concentrations of the penicillins in the blood and cerebrospinal fluid. The effect of this agent on active secretion of these antibiotics from the eye and biliary tract is minimal. While elimination of the penicillins from the body takes place largely via renal excretion, penicillin V and oxacillin are extensively degraded as well. In contrast to the situation with respect to 'natural' and 'broad-spectrum' penicillins, the serum half-life of the isoxazolyl congeners and nafcillin is only minimally prolonged in the presence of renal failure. These agents are only weakly haemodialyzable, while the other penicillins are rapidly removed from the circulation by this procedure.
Administration, Oral↗
Penetration of clindamycin phosphate into the abnormal human biliary tract.
Clindamycin phosphate, 600 mg, was given intravenously to 14 patients undergoing biliary tract surgery. Seven had complete obstruction of the common bile duct. Concentrations of total and active (nonesterified) antibiotic were measured in serum, gall bladder and common duct bile, gall bladder wall, and liver. Persons with patent common ducts had high levels of active drug at all hepatobiliary sites; concentrations were two and one half to three times higher in bile and liver than in serum. Persons with obstruction of the common duct had no measurable drug in bile and had reduced levels in gall bladder wall; however, concentrations in the liver were slightly higher than those in the group without obstruction. The results of this study suggest that, even in the presence of common duct obstruction, the concentrations of active clindamycin in the liver may be sufficient to limit the spread of intrahepatic infections due to susceptible organisms.
Anti-Bacterial Agents↗