Distribution of Ciprofloxacin into the Central Nervous System in Rats with Acute Renal or Hepatic Failure

Naora, Kohji; Ichikawa, Nobuhiro; Hirano, Hidenari; Iwamoto, Kikuo

doi:10.1211/0022357991772718

Cited by 18 publications

(11 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This delay in the elimination of the drug may be the result of renal abnormalities caused by uranyl nitrate; this result agreed with [29], that observed the prolongation in the elimination half-life of ciprofloxacin in uranyl nitrate-treated rats when compared with those in the normal rats. A longer mean residence time (MRT) was found in renal damaged ducks as compared to healthy ones.…”

Section: Discussionsupporting

confidence: 91%

“…Apparent differences were observed in pharmacokinetics parameters of ciprofloxacin between patients with severe impairment of renal function and those with normal renal function, AUC was increased, Cl was reduced, and t 1/2( β ) was prolonged in impaired renal function patients [31]. Also, in uranyl nitrate-treated rats, Cl was reduced compared with those in the normal rats [29]. …”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

Aboubakr

Soliman

2014

Veterinary Medicine International

View full text Add to dashboard Cite

The pharmacokinetics aspects of levofloxacin were studied in healthy and experimentally renal damaged Muscovy ducks after single intravenous (IV) and oral (PO) dose of 10 mg kg−1 bwt. Following IV administration, elimination half-life (t 1/2(β)) and mean residence time (MRT) were longer in renal damaged ducks than in healthy ones. Total clearance (Cltot) in renal damaged ducks (0.20 L kg−1 h−1) was significantly lower as compared to that in healthy ones (0.41 L kg−1 h−1). Following PO administration, the peak serum concentration (C max) was higher in renal damaged than in healthy ducks and was achieved at maximum time (t max) of 2.47 and 2.05 h, respectively. The drug was eliminated (t 1/2(el)) at a significant slower rate (3.94 h) in renal damaged than in healthy ducks (2.89 h). The pharmacokinetic profile of levofloxacin is altered in renal damaged ducks due to the increased serum levofloxacin concentrations compared with that in clinically healthy ducks. Oral administration of levofloxacin at 10 mg kg−1 bwt may be highly efficacious against susceptible bacteria in ducks. Also, the dose of levofloxacin should be reduced in renal damaged ducks. Pharmacokinetic/pharmacodynamic integration revealed significantly higher values for C max/MIC and AUC/MIC ratios in renal damaged ducks than in healthy ones, indicating the excellent pharmacokinetic characteristics of levofloxacin in renal damaged ducks.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

Aboubakr

Soliman

2014

Veterinary Medicine International

View full text Add to dashboard Cite

show abstract

“…Thus, CCl 4 -treated rats are widely used as common pathological models of acute hepatic failure in pharmacokinetic experiments. [10][11][12][13][14][15][16][17][18] Marked elevation in the activities of ALT and AST was confirmed in CCl 4 -treated rats, indicating the development of liver injury. CCl 4 intoxication is involved in reducing hepatic blood flow as well as the activities of hepatic enzymes responsible for drug metabolism, 14,19) and it has been reported that the elimination clearance of many drugs that undergo hepatic removal is markedly reduced in CCl 4 -treated rats.…”

Section: Discussionmentioning

confidence: 86%

Pharmacokinetic Behavior of Micafungin in Rats with Carbon Tetrachloride-Induced Acute Hepatic Failure

Konishi

Sudo

Sumi

et al. 2005

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Micafungin is a novel, semisynthetic antifungal lipopeptide with an echinocandin-like chemical structure. This agent exerts its fungicidal action by inhibiting biosynthesis of 1,3-b-D-glucan, an essential component of the cell wall of most pathogenic fungi, leading to osmotic instability, and ultimately, cell rupture.1-3) Micafungin demonstrates potent antifungal activities against Candida spp. and Aspergillus spp. in vitro, and its therapeutic efficacy has been confirmed in the treatment of infectious disease caused by these fungi species.4,5) Because of its poor intestinal absorbability, micafungin is administered via an intravenous route in clinical practice. As urinary recovery of the unchanged form is less than 1% of the total dose, it is believed that micafungin is eliminated mainly by non-renal removal. 6,7) In view of the severity of disease conditions requiring antifungal therapy, micafungin is often administered to critically ill patients with hepatic damage. However, there have not been any reports regarding the impact of hepatic dysfunction on the disposition of micafungin, even though the total body clearance is probably dependent on the metabolic capacity of the liver.In the present study, we examined the pharmacokinetic behavior of intravenously administered micafungin in acute hepatic failure in a rat model intoxicated with carbon tetrachloride (CCl 4 ). MATERIALS AND METHODSReagents Standard solutions of micafungin and FR195743 (internal standard (IS) for HPLC) were generously donated by Fujisawa Pharmaceutical Co., Ltd. (Osaka, Japan). Sodium salt of micafungin for injection (Funguard TM , containing 50 mg micafungin per a vial) and cyclosporine for injection (Sandimmun TM , containing 250 mg cyclosporine per 5 ml ampoule) were purchased from Fujisawa Pharmaceutical Co., Ltd. and Novartis Pharma KK (Tokyo, Japan), respectively. CCl 4 was obtained from Attest (Kyoto, Japan). All other chemicals and solvents were of the highest quality commercially available.Experimental Animals and Treatment Male SpragueDawley rats were obtained from CLEA Japan, Inc (Tokyo, Japan). The rats were acclimatized for at least 2 d before assignment to experimental groups at 5-6 weeks of age (140-190 g), and were housed in a clean room maintained at 23Ϯ2°C with a relative humidity 55Ϯ10% and 12-h light/dark cycle. They were allowed free access to regular animal diet and drinking water except when fasted for 24 h before administration of micafungin. Acute hepatic failure in rats was induced by intraperitoneal injection of 50 % CCl 4 in olive oil (5 ml/kg) 24 h before administration of micafungin. The rats used in this study were handled in accordance with the Guidelines for Animal Experimentation of Shiga University of Medical Science, and the experimental protocol was approved by the Animal Care and Use Committee of the Research Center for Animal Life Science of this institution.Administration of Micafungin and Blood Collection Rats were anesthetized by ethyl ether, and a polyethylene cannula (outer diameter, 0.8 mm; i...

show abstract

“…Acute hepatic failure induced experimentally with CCl 4 in animals is accompanied by a reduction in the renal tubular secretion of cefpiramine and impaired intestinal sugar transport, in addition to the suppression of various hepatic functions (Li et al 1990 ;Sugihara et al 1992 ;Castilla-Cortazar et al 1997). Acute renal failure induced by glycerol or uranyl nitrate also reduces the hepato-biliary transport of certain drugs, modulates the distribution of drugs into the central nervous system and decreases the activity of various hepatic microsomal enzymes (Bowmer & Yates 1984 ;Naora et al 1999). Thus, dysfunction of the liver or kidney, both important organs in the detoxification of xenobiotics, exerts a major influence on the pharmacokinetics of various drugs not only in the target organ but also in other organs.…”

Section: Introductionmentioning

confidence: 99%

Expression and function of P-glycoprotein in rats with carbon tetrachloride-induced acute hepatic failure

Huang

Murakami

Okochi

et al. 2001

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Acute hepatic failure was induced experimentally in rats by intraperitoneal injection of 2.5 mL kg(-1) carbon tetrachloride (CCl4), and the effects on the expression and function of P-glycoprotein in the liver, kidney and brain were evaluated. The CCl4 injection significantly increased the indicators of hepatic function (glutamate oxaloacetate transaminase, glutamate pyruvate transaminase), but not of renal function (blood urea nitrogen, glomerular filtration rate). In rats with acute hepatic failure, the hepatic P-glycoprotein concentration increased 1.5-fold and the ATP concentration decreased to approximately 40% that in control rats. In contrast, P-glycoprotein concentrations in the kidney and brain and ATP concentrations in the kidney remained unchanged. The in-vivo P-glycoprotein function in these tissues was suppressed as evaluated by biliary and renal secretory clearances and brain distribution of rhodamine 123, a P-glycoprotein substrate. These findings suggest that factors other than P-glycoprotein concentration are involved in the systemic suppression of P-glycoprotein function in diseased rats. In Caco-2 cells, plasma collected from CCl4-treated rats exhibited a greater inhibitory effect on P-glycoprotein-mediated transport of rhodamine 123 than that from control rats, suggesting the accumulation of an endogenous P-glycoprotein substrate/inhibitor in the plasma of diseased rats. In fact, the plasma concentration of corticosterone, an endogenous P-glycoprotein substrate, increased 2-fold in CCl4-treated rats compared with control rats. It was demonstrated that P-glycoprotein function is systemically suppressed in rats with CCl4-induced acute hepatic failure, not only in the target organ (liver), but also in other organs (kidney and brain), although the P-glycoprotein concentration remained unchanged in the kidney and brain, and increased in the liver. In the systemic suppression of the P-glycoprotein function in the diseased state, the alteration of plasma concentrations or components of endogenous P-glycoprotein-related compounds, such as corticosterone, would likely be involved.

show abstract

Distribution of Ciprofloxacin into the Central Nervous System in Rats with Acute Renal or Hepatic Failure

Cited by 18 publications

References 23 publications

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

Comparative Pharmacokinetics of Levofloxacin in Healthy and Renal Damaged Muscovy Ducks following Intravenous and Oral Administration

Pharmacokinetic Behavior of Micafungin in Rats with Carbon Tetrachloride-Induced Acute Hepatic Failure

Expression and function of P-glycoprotein in rats with carbon tetrachloride-induced acute hepatic failure

Contact Info

Product

Resources

About