Comparison of high‐performance liquid chromatography and bioassay of amphotericin B in serum

Hülsewede, J.W.; Dermoumi, Heide

doi:10.1111/j.1439-0507.1994.tb00279.x

Cited by 11 publications

(9 citation statements)

References 19 publications

(6 reference statements)

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“…After incubation of the samples for 20 h at 37°C, the diameters of the zones of inhibited growth were measured. The coefficient of correlation (r) between this assay and the high-performance liquid chromatography is 0.88 (8).…”

Section: Animalsmentioning

confidence: 94%

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Comparison of the Effects of Liposomal Amphotericin B and Conventional Amphotericin B on Propafenone Metabolism and Hepatic Cytochrome P-450 in Rats

Inselmann

Volkmann²,

Heidemann³

2000

Antimicrob Agents Chemother

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The effects of conventional amphotericin B (AmB) dissolved in sodium deoxycholate on microsomal cytochrome P-450 concentrations and propafenone metabolism to 5-hydroxy-propafenone and N-desalkylpropafenone were compared with those of liposomal AMB (Li-AMB) in rats. AmB (3 mg/kg/day, intravenously [i.v.]) given for 4 days caused a significant decrease in the concentration of hepatic microsomal cytochrome P-450 (0.43 ؎ 0.06 nmol/mg versus 0.62 ؎ 0.05 nmol/mg for the control [P < 0.05]). Following the application of Li-AMB (15 mg/kg/day, i.v.), hepatic microsomal cytochrome P-450 concentrations were unchanged at 0.64 ؎ 0.08 nmol/mg. AmB decreased ex vivo propafenone metabolism to 5-hydroxy-propafenone and Ndesalkyl-propafenone significantly. Sodium deoxycholate (the vehicle of AmB) by itself induced a significant decline of 5-hydroxy-propafenone and N-desalkyl-propafenone production, while microsomal cytochrome P-450 concentrations remained unchanged. In contrast, Li-AMB did not change the levels of production of 5-hydroxy-propafenone or of N-desalkyl-propafenone at either substrate concentration tested (50 mol and 200 mol). Microsomal AmB concentrations were significantly higher following Li-AMB application (21.1 ؎ 6.2 g/g versus 3.7 ؎ 1.4 g/g for AmB [P < 0.05]). We conclude that Li-AMB, in contrast to AmB, decreases neither hepatic microsomal cytochrome P-450 nor hepatic propafenone metabolism in rats ex vivo. Sodium deoxycholate alone decreases propafenone metabolism in a similar way to AmB, suggesting that it participates in AmB-induced disturbance of hepatic metabolic function.The polyene macrolide amphotericin B is the most effective antibiotic agent used for the treatment of systemic fungal infections in humans (13). However, its clinical use is limited due to its pronounced side effects such as chills, fever, nausea, and organ damage (especially the impairment of kidney function). Amphotericin B has a high affinity for biological membranes, resulting in binding to sterols, which is most likely responsible for its excellent antifungal properties. On the other hand, this activity may potentially alter cellular membrane functions, resulting in organ dysfunction. The distribution of amphotericin B differs widely between organs, and the highest amphotericin B concentrations are reached in the liver (2) with the potential to alter hepatic cellular integrity (12). In perfused rat livers, it has been demonstrated that amphotericin B reduces bile flow and decreases bile acid secretion (6). Studies performed with human liver microsomes suggest that amphotericin alters hepatic metabolic function and results in a decrease of antipyrine clearance (7). However, the effect of amphotericin B on hepatic metabolic function is not known in detail. To overcome the pronounced side effects of conventional amphotericin B, novel lipid-containing formulations of amphotericin B with fewer side effects have been developed. These formulations include the small unilamellar vesicle liposomal amphotericin B known as AmBisome, which has ...

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Section: Animalsmentioning

confidence: 94%

“…Individual hepatic amphotericin B concentrations were determined by using a plate diffusion bioassay (8). From each sample, 100 l of microsomal suspension was used.…”

Section: Animalsmentioning

confidence: 99%

Comparison of the Effects of Liposomal Amphotericin B and Conventional Amphotericin B on Propafenone Metabolism and Hepatic Cytochrome P-450 in Rats

Inselmann

Volkmann²,

Heidemann³

2000

Antimicrob Agents Chemother

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“…Serum samples, obtained by centrifugation of the blood at 1095 g were stored at −20°C until their use. Drug levels achieved after monotherapies were determined by bioassay, as previously described with modifications . Briefly, 22 mL of yeast nitrogen base agar maintained at 45°C was mixed with a suspension consisting of 2 × 10 6 CFU/mL of Candida albicans (ATCC 90028 for AMB and FLC determinations) or Candida kefyr (ATCC 28838 for VRC determination) and then poured into sterile Petri dishes.…”

Section: Methodsmentioning

confidence: 99%

Combined antifungal therapy against systemic murine infections by rare Cryptococcus species

Thomson

Mayayo

López-Fernández

et al. 2016

Mycoses

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Cryptococcus albidus and Cryptococcus laurentii are uncommon species of this genus that in recent decades have increasingly caused opportunistic infections in humans, mainly in immunocompromised patients; the best therapy for such infection being unknown. Using a murine model of systemic infection by these fungi, we have evaluated the efficacy of amphotericin B (AMB) at 0.8 mg/kg, administered intravenously, fluconazole (FLC) or voriconazole (VRC), both administered orally, at 25 mg/kg and the combination of AMB plus VRC against three C. albidus and two C. laurentii strains. All the treatments significantly reduced the fungal burden in all the organs studied. The combination showed a synergistic effect in the reduction in fungal load, working better than both monotherapies. The histopathological study confirmed the efficacy of the treatments.

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“…Reverse-phase chromatography analysis on a Novapack C18 reversed-phase column (3.9 by 150 mm.) was performed by previously described methods (4,18) with a liquid chromatograph equipped with a solvent delivery system control (Waters 600 E; Millipore), a Waters 717 plus Autosampler with temperature control system (4°C for AmB samples), and a photodiode array detector and reporting integrator (Waters 990). The detection was at 408 nm, corresponding to the maximum absorbance for AmB.…”

mentioning

confidence: 99%

Mechanism of Amphotericin B Resistance in Leishmania donovani Promastigotes

Mbongo

Loiseau

Billion

et al. 1998

Antimicrob Agents Chemother

175

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Amphotericin B (AmB)-resistant Leishmania donovanipromastigotes were selected by increasing drug pressure, and their biological features were compared with those of the wild-type parent strain. The 50% inhibitory concentration for resistant cells was 20 times higher than that for the wild-type. Resistance was stable after more than 40 passages in drug-free medium, and resistant promastigotes were infective to macrophages in vitro but lost their virulence in vivo. They had 2.5 times longer generation time, decreased AmB uptake, and increased AmB efflux in comparison to the wild type. Fluorescence measurement with a specific plasma membrane probe, 1-[4-(trimethylammonio)-1,6-diphenylhexa]-1,3,5-triene, showed increased membrane fluidity in drug-resistant promastigotes. Analysis of lipid composition showed that in resistant cells saturated fatty acids were prevalent, with stearic acid as the major fatty acid, and the major sterol was an ergosterol precursor, the cholesta-5, 7, 24-trien-3β-ol and not ergosterol as in the AmB-sensitive strain.

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Comparison of high‐performance liquid chromatography and bioassay of amphotericin B in serum

Cited by 11 publications

References 19 publications

Comparison of the Effects of Liposomal Amphotericin B and Conventional Amphotericin B on Propafenone Metabolism and Hepatic Cytochrome P-450 in Rats

Comparison of the Effects of Liposomal Amphotericin B and Conventional Amphotericin B on Propafenone Metabolism and Hepatic Cytochrome P-450 in Rats

Combined antifungal therapy against systemic murine infections by rare Cryptococcus species

Mechanism of Amphotericin B Resistance in Leishmania donovani Promastigotes

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