Extensión de tiempo QT
Efectos adversos de las drogas
Variantes ✨Para la evaluación computacionalmente intensiva de las variantes, elija la suscripción estándar paga.
Áreas de aplicación
Explicaciones para pacientes
No tenemos advertencias adicionales para la combinación de ciprofloxacina y indinavir. Consulte también la información especializada pertinente.
|Indinavir||1.13 [0.58,2.33] 1||1.13|
Los cambios en la exposición mencionados se refieren a cambios en la curva de concentración plasmática-tiempo [AUC]. No detectamos ningún cambio en la exposición a ciprofloxacina. Actualmente no podemos estimar la influencia de la indinavir. La exposición a indinavir aumenta al 113%, cuando se combina con ciprofloxacina (113%). El AUC está entre 58% y 233% dependiendo del
Los parámetros farmacocinéticos de la población media se utilizan como punto de partida para calcular los cambios individuales en la exposición debidos a las interacciones.
La ciprofloxacina tiene una biodisponibilidad oral media [ F ] del 70%, por lo que los niveles plasmáticos máximos [Cmax] tienden a cambiar con una interacción. La vida media terminal [ t12 ] es bastante corta a las 3.5 horas y se alcanzan rápidamente niveles plasmáticos constantes [ Css ]. La unión a proteínas [ Pb ] es muy débil al 30%. Aproximadamente el 55.0% de la dosis administrada se excreta inalterada a través de los riñones y esta proporción rara vez se modifica por las interacciones. El metabolismo tiene lugar principalmente a través de CYP1A2. y el transporte activo se realiza en parte a través de BCRP, OATP1A2 y PGP.
La indinavir tiene una biodisponibilidad oral media [ F ] del 60%, por lo que los niveles plasmáticos máximos [Cmax] tienden a cambiar con una interacción. La vida media terminal [ t12 ] es bastante corta a las 2 horas y se alcanzan rápidamente niveles plasmáticos constantes [ Css ]. La unión a proteínas [ Pb ] es bastante débil al 60% y el volumen de distribución [ Vd ] es muy grande a 78 litros, Dado que la sustancia tiene una tasa de extracción hepática baja de 0,9, el desplazamiento de la unión a proteínas [Pb] en el contexto de una interacción puede aumentar la exposición. El metabolismo tiene lugar a través de CYP2D6 y CYP3A4, entre otros. y el transporte activo se realiza en parte a través de MRP2 y PGP.
|Efectos serotoninérgicos a||0||Ø||Ø|
Clasificación: Según nuestro conocimiento, ni la ciprofloxacina ni la indinavir aumentan la actividad serotoninérgica.
|Kiesel & Durán b||0||Ø||Ø|
Clasificación: Según nuestros hallazgos, ni la ciprofloxacina ni la indinavir aumentan la actividad anticolinérgica.
Extensión de tiempo QT
Clasificación: La ciprofloxacina potencialmente puede causar arritmias ventriculares torsades de pointes. No conocemos ningún potencial de prolongación del intervalo QT para la indinavir.
Efectos secundarios generales
|Efectos secundarios||∑ frecuencia||cip||ind|
|Dolor abdominal||9.3 %||n.a.||9.3|
|Dolor de cabeza||8.8 %||3.0||6.0|
|Sentido del gusto alterado||4.3 %||n.a.||4.3|
|Pérdida de apetito||3.0 %||n.a.||3.0|
Secreción nasal (3%): ciprofloxacina
Dispepsia (2.9%): indinavir
Diarrea por clostridium difficile: ciprofloxacina
Hemorragia gastrointestinal: ciprofloxacina
Erupción (1.8%): ciprofloxacina
Necrolisis epidérmica toxica: ciprofloxacina
Eritema multiforme: indinavir
Síndrome de Stevens-Johnson: indinavir, ciprofloxacina
Nefritis tubulointersticial: indinavir, ciprofloxacina
Cistitis hemorrágica: ciprofloxacina
Insuficiencia renal: ciprofloxacina
Infarto de miocardio: ciprofloxacina
Insuficiencia hepática: ciprofloxacina
Reacción de hipersensibilidad: ciprofloxacina
Cetoacidosis diabética: indinavir
Alteración de la atención: ciprofloxacina
Síndrome de Guillain-Barré: ciprofloxacina
Deterioro de la memoria: ciprofloxacina
Neuropatía periférica: ciprofloxacina
Pseudotumor cerebri: ciprofloxacina
Presión intracraneal elevada: ciprofloxacina
Anemia hemolítica: indinavir, ciprofloxacina
Anemia aplásica: ciprofloxacina
Diabetes mellitus: indinavir
Miastenia gravis: ciprofloxacina
Rotura de tendón: ciprofloxacina
Aneurisma aortico: ciprofloxacina
Con base en sus
Referencias de literatura
Abstract: The pharmacokinetics of intravenous ciprofloxacin and its metabolites were characterized in 42 subjects with various degrees of renal function (group 1, Clcr (mL/min/1.73 m2) > 90, n = 10; group 2, Clcr 61-90, n = 11; group 3, Clcr 31-60, n = 11; group 4, Clcr < or = 30, n = 10). The dosage regimens were-groups 1 and 2: 400 mg i.v. at 8 hourly intervals; group 3: 400 mg i.v. at 12 hourly intervals and group 4: 300 mg i.v. at 12 hourly intervals. Subjects received a single dose on days 1 and 5 and multiple doses on days 2-4. Multiple plasma and urine samples were collected on days 1 and 5 for the analysis of ciprofloxacin and its metabolites (M1, M2 and M3). Plasma concentrations (Cmax and AUC) of ciprofloxacin and its M1 and M2 metabolites were significantly increased in subjects with reduced Clcr values (Clcr < 60 mL/min/1.73 m2) compared with normal subjects (Clcr > 90 mL/min/1.73 m2). A positive correlation was observed between ciprofloxacin clearance (Cl) and Clcr with a slope of 0.29 (r2 = 0.78) and between renal clearance (Clr) and Clcr with a slope of 0.19 (r2 = 0.84). For patients with severe infections a dosage regimen of 400 mg iv 8 hourly is appropriate in patients with Clcr > 60 mL/min/1.73 m2. In patients with Clcr values of 31-60 mL/min/1.73 m2 a dosage regimen of 400 mg 12 hourly provides similar plasma concentrations to those observed for subjects with Clcr 61-90 mL/min/1.73 m2 receiving 400 mg 8 hourly. Based on modeling of the plasma concentrations in subjects with Clcr < or = 30 ml/min/1.73 m2, a dosage regimen of 400 mg every 24 h will provide plasma concentrations similar to those observed in subjects with Clcr between 61-90 mL/min/1.73 m2 given 400 mg every 8 h.
Abstract: The pharmacokinetic interaction between indinavir and ritonavir was evaluated in five groups of healthy adult volunteers to explore the potential for twice-daily (b.i.d.) dosing of this combination. All subjects received 800 mg of indinavir every 8 h (q8h) on day 2. In addition, subjects in group I received one dose of 800 mg of indinavir on day 1 and 800 mg of indinavir q8h on day 17. Subjects in Groups II and IV each received one dose of 600 mg of indinavir on days 1 and 17, and subjects in groups III and V each received one dose of 400 mg of indinavir on days 1 and 17. During days 3 to 17, ritonavir placebo or ritonavir at 200, 300, 300, or 400 mg q12h was given to groups I, II, III, IV, and V, respectively. Ritonavir at steady state probably inhibited the cytochrome P-450 3A metabolism of indinavir and substantially increased plasma indinavir concentrations, with the area under the plasma concentration-time curve (AUC) increasing up to 475% and the peak concentration in serum (Cmax) increasing up to 110%. The Cmax/trough concentration ratio decreased from 50 in standard q8h regimens to less than 14 when indinavir was administered with ritonavir. For a constant indinavir dose, an increase in the ritonavir dose yielded similar indinavir AUCs, Cmaxs, and concentrations at 12 h (C12s). For a constant ritonavir dose, an increase in the indinavir dose resulted in approximately proportional increases in the indinavir AUC, less than proportional increases in Cmax, and slightly more than proportional increases in C12. Ritonavir reduced between-subject variability in the indinavir AUC and trough concentrations and did not affect indinavir renal clearance. With the altered pharmacokinetic profile, indinavir likely could be given as a b.i.d. combination regimen with ritonavir. This could potentially improve patient compliance and thereby reduce treatment failures.
Abstract: STUDY OBJECTIVE: To compare the rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin administration. DESIGN: Retrospective database analysis. INTERVENTION: Evaluation of reported rates of torsades de pointes in patients who received these quinolones between January 1, 1996, and May 2, 2001. MEASUREMENTS AND MAIN RESULTS: In the United States, 25 cases of torsades de pointes associated with these quinolones (ciprofloxacin 2, ofloxacin 2, levofloxacin 13, gatifloxacin 8, moxifloxacin 0) were identified. Ciprofloxacin was associated with a significantly lower rate of torsades de pointes (0.3 cases/10 million prescriptions, 95% confidence interval [CI] 0.0-1.1) than levofloxacin (5.4/10 million, 95% CI 2.9-9.3, p<0.001) or gatifloxacin (27/10 million, 95% CI 12-53, p<0.001 for comparison with ciprofloxacin or levofloxacin). When the analysis was limited to the first 16 months after initial U.S. approval of the agent, the rates for levofloxacin (16/10 million) and gatifloxacin (27/10 million) were similar (p>0.5). CONCLUSION: Levofloxacin should be administered with caution in patients with risk factors for QT prolongation. Gatifloxacin should be avoided in the same patient population, and the recommended dosage of 400 mg/day should not be exceeded.
Abstract: Ciprofloxacin has been widely used for treating infections and has been found to have very low cardiovascular side effects. QTc prolongation with the use of ciprofloxacin is yet to be reported in literature. A case report highlighting QTc prolongation by use of ciprofloxacin is being presented.
Abstract: No Abstract available
Abstract: AIMS: The aim of the study was to characterize the population pharmacokinetics of indinavir, define the relationship between the pharmacokinetics of indinavir and ritonavir, and to identify the factors influencing the pharmacokinetics of indinavir alone or when given with ritonavir. METHODS: HIV-1-infected patients being treated with an indinavir-containing regimen were included. During regular visits, 102 blood samples were collected for the determination of plasma indinavir and ritonavir concentrations. Full pharmacokinetic curves were available from 45 patients. Concentrations of indinavir and ritonavir were determined by liquid chromatography coupled with electrospray tandem mass spectrometry. Pharmacokinetic analysis was performed using nonlinear mixed effect modelling (NONMEM). RESULTS: The disposition of indinavir was best described by a single compartment model with first order absorption and elimination. Values for the clearance, volume of distribution and the absorption rate constant were 46.8 l h(-1) (24.2% IIV), 82.3 l (24.6% IIV) and 02.62 h(-1), respectively. An absorption lag-time of 0.485 h was detected in patients also taking ritonavir. Furthermore this drug, independent of dose (100-400 mg) or plasma concentration, decreased the clearance of indinavir by 64.6%. In contrast, co-administration of efavirenz or nevirapine increased the clearance of indinavir by 41%, irrespective of the presence or absence of ritonavir. Female patients had a 48% higher apparent bioavailability of indinavir than males. CONCLUSIONS: The pharmacokinetic parameters of indinavir were adequately described by our population model. Female gender and concomitant use of ritonavir and non-nucleoside reverse transcriptase inhibitors strongly influenced the pharmacokinetics of this drug. The results support the concept of ritonavir boosting, maximum inhibition of indinavir metabolized being observed at 100 mg.
Abstract: The new respiratory fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, and on the horizon, garenoxacin) offer many improved qualities over older agents such as ciprofloxacin. These include retaining excellent activity against Gram-negative bacilli, with improved Gram-positive activity (including Streptococcus pneumoniae and Staphylococcus aureus). In addition, gatifloxacin, moxifloxacin and garenoxacin all demonstrate increased anaerobic activity (including activity against Bacteroides fragilis). The new fluoroquinolones possess greater bioavailability and longer serum half-lives compared with ciprofloxacin. The new fluoroquinolones allow for once-daily administration, which may improve patient adherence. The high bioavailability allows for rapid step down from intravenous administration to oral therapy, minimizing unnecessary hospitalization, which may decrease costs and improve quality of life of patients. Clinical trials involving the treatment of community-acquired respiratory infections (acute exacerbations of chronic bronchitis, acute sinusitis, and community-acquired pneumonia) demonstrate high bacterial eradication rates and clinical cure rates. In the treatment of community-acquired respiratory tract infections, the various new fluoroquinolones appear to be comparable to each other, but may be more effective than macrolide or cephalosporin-based regimens. However, additional data are required before it can be emphatically stated that the new fluoroquinolones as a class are responsible for better outcomes than comparators in community-acquired respiratory infections. Gemifloxacin (except for higher rates of hypersensitivity), levofloxacin, and moxifloxacin have relatively mild adverse effects that are more or less comparable to ciprofloxacin. In our opinion, gatifloxacin should not be used, due to glucose alterations which may be serious. Although all new fluoroquinolones react with metal ion-containing drugs (antacids), other drug interactions are relatively mild compared with ciprofloxacin. The new fluoroquinolones gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin have much to offer in terms of bacterial eradication, including activity against resistant respiratory pathogens such as penicillin-resistant, macrolide-resistant, and multidrug-resistant S. pneumoniae. However, ciprofloxacin-resistant organisms, including ciprofloxacin-resistant S. pneumoniae, are becoming more prevalent, thus prudent use must be exercised when prescribing these valuable agents.
Abstract: Fluoroquinolone antimicrobial drugs are absorbed efficiently after oral administration despite of their hydrophilic nature, implying an involvement of carrier-mediated transport in their membrane transport process. It has been that several fluoroquinolones are substrates of organic anion transporter polypeptides OATP1A2 expressed in human intestine derived Caco-2 cells. In the present study, to clarify the involvement of OATP in intestinal absorption of ciprofloxacin, the contribution of Oatp1a5, which is expressed at the apical membranes of rat enterocytes, to intestinal absorption of ciprofloxacin was investigated in rats. The intestinal membrane permeability of ciprofloxacin was measured by in situ and the vascular perfused closed loop methods. The disappeared and absorbed amount of ciprofloxacin from the intestinal lumen were increased markedly in the presence of 7,8-benzoflavone, a breast cancer resistance protein inhibitor, and ivermectin, a P-glycoprotein inhibitor, while it was decreased significantly in the presence of these inhibitors in combination with naringin, an Oatp1a5 inhibitor. Furthermore, the Oatp1a5-mediated uptake of ciprofloxacin was saturable with a K(m) value of 140 µm, and naringin inhibited the uptake with an IC(50) value of 18 µm by Xenopus oocytes expressing Oatp1a5. Naringin reduced the permeation of ciprofloxacin from the mucosal-to-serosal side, with an IC(50) value of 7.5 µm by the Ussing-type chamber method. The estimated IC(50) values were comparable to that of Oatp1a5. These data suggest that Oatp1a5 is partially responsible for the intestinal absorption of ciprofloxacin. In conclusion, the intestinal absorption of ciprofloxacin could be affected by influx transporters such as Oatp1a5 as well as the efflux transporters such as P-gp and Bcrp.
Abstract: Besides logistical and ethical concerns, evaluation of safety and efficacy of medications in pregnant women is complicated by marked changes in pharmacokinetics (PK) of drugs. For example, CYP3A activity is induced during the third trimester (T3). We explored whether a previously published physiologically based pharmacokinetic (PBPK) model could quantitatively predict PK profiles of CYP3A-metabolized drugs during T3, and discern the site of CYP3A induction (i.e., liver, intestine, or both). The model accounted for gestational age-dependent changes in maternal physiological function and hepatic CYP3A activity. For model verification, mean plasma area under the curve (AUC), peak plasma concentration (Cmax), and trough plasma concentration (Cmin) of midazolam (MDZ), nifedipine (NIF), and indinavir (IDV) were predicted and compared with published studies. The PBPK model successfully predicted MDZ, NIF, and IDV disposition during T3. A sensitivity analysis suggested that CYP3A induction in T3 is most likely hepatic and not intestinal. Our PBPK model is a useful tool to evaluate different dosing regimens during T3 for drugs cleared primarily via CYP3A metabolism.CPT: Pharmacometrics & Systems Pharmacology (2012) 1, e3; doi:10.1038/psp.2012.2; advance online publication 26 September 2012.
Abstract: Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers.