Effect of hyperlipidemia on ketoconazole–midazolam drug–drug interaction in rat

Hamdy, Dalia A.; Brocks, Dion R.

doi:10.1002/jps.22675

Cited by 10 publications

(13 citation statements)

References 35 publications

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“…In HL and IHL protein-binding tests, the ultrafiltration devices were pre-incubated with 5% Triton ® (X-100) for 12 h to overcome the binding of drugs and lipids to the filter. The devices were then used after being rinsed several times with double-distilled water [16, 22]. …”

Section: Methodsmentioning

confidence: 99%

“…Hyperlipidemia is a chronic disease characterized by high plasma lipoprotein levels [5, 16, 41]. The risk factors of hyperlipidemia include genetic makeup defects, unhealthy diet, sedentary lifestyle habits, and certain drugs or diseases [15].…”

Section: Introductionmentioning

confidence: 99%

“…Hyperlipidemia is accompanied by a consistent increase in low-density lipoprotein that is a key contributor to an increased risk of atherosclerosis, hypertension, and ischemic heart disease [17, 30]. Furthermore, hyperlipidemia was shown to result in alterations in the pharmacokinetic and pharmacodynamics pattern of some drugs [1, 16, 22, 34, 37]. This may be attributed to reduced unbound fraction, enhanced lipoprotein receptor-mediated drug tissue uptake, and/or altered metabolizing enzyme expression [15, 17, 22, 34].…”

Section: Introductionmentioning

confidence: 99%

“…Ketoconazole is another azole antifungal whose pharmacokinetic parameters were not affected by hyperlipidemia in rats. However, its liver uptake was altered and the severity of its drug interaction with midazolam was increased [16]. Whether hyperlipidemia could potentiate or reduce the severity of the drug interaction between PSZ and VCR is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Hyperlipidemia Alters the Pharmacokinetics of Posaconazole and Vincristine Upon Co-Administration in Rats

et al. 2017

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ObjectivesCo-administration of posaconazole (PSZ) and vincristine (VCR) in the treatment of patients with acute lymphoblastic leukemia increases the neurotoxicity of VCR. Our aim is to study the effect of increased lipoprotein levels on the pharmacokinetics of PSZ and VCR upon co-administration in rats.MethodsRats were assigned to three groups, normolipidemic (NL), intermediate hyperlipidemic (IHL), and extreme hyperlipidemic (HL) groups. All rats were administered PSZ orally followed by VCR intravenously 4 h later. For the pharmacokinetic study, serial plasma samples were collected over 96 h and for tissue distribution study; plasma, lung, and liver tissues were collected over 48 h post oral dosing.ResultsPosaconazole showed higher plasma concentrations than VCR at all time points. Co-administration of VCR with PSZ reduced PSZ weight normalized oral clearance, increased PSZ area under the plasma concentration–time curve (AUC) from time zero to infinity, showed higher PSZ liver concentrations, and increased VCR volume of distribution of the central compartment. Upon increasing the lipoprotein levels, PSZ showed higher plasma availability and delayed tissue distribution, whereas VCR had shown a significant decrease in PSZ AUC0-24h, AUC0-tlast, and AUCo-inf (NL = IHL > HL) and a significant increase in the volume of distribution (NL = IHL < HL). Vincristine has shown higher tissue uptake and concentrations.ConclusionMonitoring cholesterol and triglyceride levels in patients with acute lymphoblastic leukemia is advisable to decrease VCR neurological side effect incidences and delay the activity of both PSZ and VCR.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hyperlipidemia Alters the Pharmacokinetics of Posaconazole and Vincristine Upon Co-Administration in Rats

et al. 2017

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“…The day before the experiment, the jugular veins of the rats were catheterized with a cannula under isoflurane anesthesia delivered by anesthetic machine as previously described (Hamdy and Brocks 2011). The cannula was filled with 100 u/mL heparin in saline then capped.…”

Section: Surgery Met Dosing and Sample Collectionmentioning

confidence: 99%

Pharmacokinetics of metformin in the rat: assessment of the effect of hyperlipidemia and evidence for its metabolism to guanylurea

Gabr

El-Sherbeni

Ben‐Eltriki

et al. 2017

Can. J. Physiol. Pharmacol.

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Metformin pharmacokinetics are highly dependent upon organic cationic transporters. There is evidence of a change in its renal clearance in hyperlipidemic obese patients, and no information on its metabolic fate. To study some of these aspects, the influence of poloxamer 407 (P407)-induced hyperlipidemia on metformin pharmacokinetics was assessed. Control and P407 treated adult male rats were administered 30 mg/kg metformin intravenously (iv). The pharmacokinetic assessments were performed at 2 time points, 36 and 108 h, following the intraperitoneal dose of P407 (1 g/kg). mRNA and protein expressions of cationic drug transporters were also measured.There was no evidence of a change in metformin pharmacokinetics after iv doses as a consequence of short term hyperlipidemia, and a change in transporter mRNA but not protein expression in the 108 h post-P407 treated rats. Urinary recovery of unchanged drug was high (> 90%) but incomplete. Presumed metabolite peaks were detected in chromatograms of hepatocytes and microsomal protein spiked with metformin. Comparative chromatographic elution times and mass spectra suggested that one of the predominant metabolites was guanylurea. Hyperlipidemia by itself did not affect the pharmacokinetics of metformin.Guanylurea is a putative metabolite of metformin in rats.

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Ammonia‐oxidizing bacteria dominates over ammonia‐oxidizing archaea in a saline nitrification reactor under low DO and high nitrogen loading

Zhang

2011

Biotech & Bioengineering

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A continuous nitrification reactor treating saline wastewater was operated for almost 1 year under low dissolved oxygen (DO) levels (0.15-0.5 mg/L) and high nitrogen loadings (0.26-0.52 kg-N/(m(3) day)) in four phases. The diversity and abundance of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) were analyzed by cloning, terminal restriction fragment length polymorphism (T-RFLP) and quantitative polymerase chain reaction (qPCR). The results showed that there were only one dominant AOA species and one dominant AOB species in the reactor in all of the four experimental phases. The amoA gene of the dominant AOA only had a similarity of 89.3% with the cultured AOA species Nitrosopumilus maritimus SCM1. All of the AOB species detected in the reactor belong to Nitrosomonas genus and it was found that the AOB populations changed with the ammonium loadings and DO levels. The abundance of AOB in the reactor was ∼40 times larger than that of AOA, and the ratio of AOB to AOA increased significantly up to ∼2,000 to ∼4,000 with the increase of ammonium loading, indicating that AOB are much more competitive than AOA in high ammonium environments and probably AOA play a less important role than AOB in the nitrification reactors.

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Effect of hyperlipidemia on ketoconazole–midazolam drug–drug interaction in rat

Cited by 10 publications

References 35 publications

Hyperlipidemia Alters the Pharmacokinetics of Posaconazole and Vincristine Upon Co-Administration in Rats

Hyperlipidemia Alters the Pharmacokinetics of Posaconazole and Vincristine Upon Co-Administration in Rats

Pharmacokinetics of metformin in the rat: assessment of the effect of hyperlipidemia and evidence for its metabolism to guanylurea

Ammonia‐oxidizing bacteria dominates over ammonia‐oxidizing archaea in a saline nitrification reactor under low DO and high nitrogen loading

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