RESUMEN
This first-in-human, phase I study evaluated the safety, tolerability, pharmacokinetic and pharmacodynamic profile of ASKP1240 in healthy subjects. Twelve sequential groups (each 6 active and 3 placebo) were randomly assigned to placebo or single ascending doses of intravenous ASKP1240 (0.00003-10 mg/kg). ASKP1240 exhibited nonlinear pharmacokinetics, with mean maximal serum concentrations and area under the serum concentration-time curves ranging from 0.7 to 251.6 µg/mL and 6.5 to 55409.6 h·µg/mL following doses 0.1 mg/kg-10 mg/kg, respectively. CD40 receptor occupancy by ASKP1240, which was dose-dependent, reached a maximum at doses above 0.01 mg/kg. ASKP1240 was well tolerated, with no evidence of cytokine release syndrome or thromboembolic events. Treatment emergent antibodies to ASKP1240 were detected in 5/70 (7.1%) ASKP1240 recipients. In conclusion, antagonism of the CD40/CD154 interaction with ASKP1240 was safe and well tolerated at the doses tested.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/farmacocinética , Antígenos CD40/antagonistas & inhibidores , Antígenos CD40/metabolismo , Inmunosupresores/farmacología , Inmunosupresores/farmacocinética , Adolescente , Adulto , Área Bajo la Curva , Coagulación Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Voluntarios Sanos , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto JovenRESUMEN
Given the risk of central nervous system infection, relatively high weight-based echinocandin dosages may be required for the successful treatment of invasive candidiasis and candidemia in young infants. This open-label study assessed the safety and pharmacokinetics (PK) of micafungin in 13 young infants (>48 h and <120 days of life) with suspected candidemia or invasive candidiasis. Infants of body weight > or =1,000 and <1,000 g received 7 and 10 mg/kg/day, respectively, for a minimum of 4-5 days. In the 7-mg/kg/day group, the mean baseline weight and gestational age were 2,101 g and 30 weeks, respectively; in the 10-mg/kg/day group, they were 688 g and 25 weeks, respectively. The median pharmacokinetic values for the 7- and 10-mg/kg/day groups, respectively, were as follows: area under the concentration-time curve from 0 to 24 h (AUC(0-24)), 258.1 and 291.2 microg x h/ml; clearance at steady state adjusted for body weight, 0.45 and 0.57 ml/min/kg; maximum plasma concentration, 23.3 and 24.9 micro g/ml; and volume of distribution at steady state adjusted for body weight, 341.4 and 542.8 ml/kg. No deaths or discontinuations from treatment occurred. These data suggest that micafungin dosages of 7 and 10 mg/kg/day are well tolerated and provide exposure levels that have been shown (in animal models) to be adequate for central nervous system coverage.
Asunto(s)
Equinocandinas/efectos adversos , Equinocandinas/farmacocinética , Lipopéptidos/efectos adversos , Lipopéptidos/farmacocinética , Factores de Edad , Candidiasis/sangre , Candidiasis/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Equinocandinas/administración & dosificación , Femenino , Humanos , Lactante , Recién Nacido , Lipopéptidos/administración & dosificación , Masculino , MicafunginaRESUMEN
The pharmacokinetics, safety and tolerability of a once-daily formulation of tacrolimus (tacrolimus extended-release formulation; XL formerly referred to as MR or MR4) were assessed in 18 stable pediatric liver transplant recipients who were converted from the twice-a-day formulation of tacrolimus (TAC) to XL. Patients received their twice-a-day dose of TAC on study days 1 through 7. Beginning on the morning of study day 8, patients were converted to XL on a 1:1 (mg:mg) basis for their total daily dose, and were maintained on a once-daily AM dosing regimen using the same therapeutic monitoring and patient care techniques employed with TAC. Based on pharmacokinetic profiles obtained on study days 7 (TAC) and 14 (XL), steady state exposure (AUC(0-24)) was equivalent between XL and TAC; the mean XL/TAC ratio for lnAUC(0-24) was 100.9% (90% CI: 90.8%, 112.1%). AUC(0-24) and C(min) were strongly correlated at steady state (correlation coefficient: XL 0.90, TAC 0.94). During the first year post-conversion, there were no cases of acute rejection, discontinuation of XL, graft loss or death. The safety profile of XL was consistent with that known for TAC. These results support the safe and convenient conversion of pediatric liver transplant recipients from twice-a-day TAC to once-daily XL.
Asunto(s)
Trasplante de Hígado/inmunología , Tacrolimus/uso terapéutico , Adolescente , Área Bajo la Curva , Niño , Preescolar , Preparaciones de Acción Retardada , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/farmacocinética , Inmunosupresores/uso terapéutico , Masculino , Tacrolimus/administración & dosificación , Tacrolimus/farmacocinética , Factores de TiempoRESUMEN
We assessed the pharmacokinetics and interactions of steady-state micafungin (Mycamine) or placebo with steady-state voriconazole in 35 volunteers. The 90% confidence intervals around the least-squares mean ratios for micafungin pharmacokinetic parameters and placebo-corrected voriconazole pharmacokinetic parameters were within the 80%-to-125% limits, indicating an absence of drug interaction.
Asunto(s)
Antifúngicos/farmacocinética , Lipoproteínas/farmacocinética , Péptidos Cíclicos/farmacocinética , Pirimidinas/farmacocinética , Triazoles/farmacocinética , Administración Oral , Adolescente , Adulto , Antifúngicos/administración & dosificación , Esquema de Medicación , Interacciones Farmacológicas , Quimioterapia Combinada , Equinocandinas , Femenino , Humanos , Lipopéptidos , Lipoproteínas/administración & dosificación , Masculino , Micafungina , Persona de Mediana Edad , Péptidos Cíclicos/administración & dosificación , Pirimidinas/administración & dosificación , Triazoles/administración & dosificación , VoriconazolRESUMEN
PURPOSE: The objective of this investigation is to develop a rational design of Osteotropic Drug Delivery System (ODDS), which we have proposed as a novel method for drug delivery to the skeleton via bisphosphonic prodrug, based on the relationship between physicochemical and pharmacokinetic properties of bisphosphonates. METHODS: The theoretical octanol/water partition coefficients (clog P) of 13 bisphosphonates were calculated by computer software, CLOGP ver. 3.05 (Daylight C.I.S., Inc. Irvine, CA) and related to pharmacokinetic or osteotropic parameters after intravenous injection into rats. On the other hand, to optimize ODDS of diclofenac (DIC-BP), the effects of doses or infusion rates on the in vivo disposition were investigated in relation to solubility product value (Ksp) of DIC-BP-calcium complex. RESULTS: Clog P had good correlations with total plasma clearance, apparent distribution volume and the fraction dose delivered to the whole skeleton after bolus injection into rats (r = -0.868 approximately -0.914). The targetability of bisphosphonates to the skeleton was linearly decreased with an increase in clog P value and the more hydrophilic bisphosphonates were suitable for ODDS in bolus administration. On the other hand, DIC-BP, a relatively lipophilic bisphosphonate, was effectively and selectively delivered to the skeleton only when administered as a slow infusion to keep plasma concentration lower than that calculated from Ksp value where DIC-BP could precipitate with calcium in the plasma circulation. CONCLUSIONS: Our results suggest the possibility of a rational design of ODDS via bisphosphonic prodrugs, after consideration of compound lipophilicity and precipitability of bisphosphonate-calcium complex.
Asunto(s)
Huesos/efectos de los fármacos , Difosfonatos/farmacología , Algoritmos , Animales , Fenómenos Químicos , Química Física , Difosfonatos/administración & dosificación , Lípidos/química , Hígado/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Solubilidad , Bazo/metabolismoAsunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Calcineurina/metabolismo , Rechazo de Injerto/fisiopatología , Inmunosupresores/farmacología , Trasplante de Órganos , Animales , Inhibidores de la Calcineurina , Ciclosporina/farmacología , Ciclosporina/uso terapéutico , Interacciones Farmacológicas , Resistencia a Múltiples Medicamentos , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacología , Ácido Micofenólico/uso terapéutico , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Inmunología del TrasplanteRESUMEN
The extracellular Lipases A and C produced by Geotrichum sp. FO401B have a preference for the sn-1,3 and sn-2 positions of triglyceride, respectively. Total production of these lipases was increased by plant oils and tributyrin. Butyl Toyopearl column chromatography demonstrated that only Lipase C was produced in the presence of tributyrin. Lipase C hydrolysed natural fats except sardine oil preferentially at the sn-2 position, but it showed little stereoselectivity for triolein.
Asunto(s)
Geotrichum/efectos de los fármacos , Lipasa/metabolismo , Triglicéridos/metabolismo , Triglicéridos/farmacología , Inducción Enzimática , Geotrichum/enzimología , Lipasa/biosíntesis , Especificidad por Sustrato , Triglicéridos/químicaRESUMEN
The effect of three positional isomers, o-, m- and p-acetylaminophenyl sulfate (AOAPS, AMAPS and APAPS (acetaminophen sulfate), respectively), on the pharmacokinetics of acetaminophen (APAP) was investigated in rats. All of the intravenously administered positional isomers were rapidly eliminated from plasma, and approximately 80% of the dose was excreted in an unchanged form in the urine within 4 h, while biliary excretions represented a small percent of the doses. Following the intravenous bolus injection of APAP, plasma elimination of APAP was accelerated and the distribution volume of APAP was increased under a steady state concentration (about 10 microg APAP eq/ml) of AOAPS or APAPS, but not AMAPS, as compared with saline infusion. Total body clearances of APAP were increased from 18.3 ml/min/kg for the control to 23.9 and 26.9 ml/min/kg for AOAPS and APAPS coadministration, respectively. AOAPS and APAPS competitively displaced the serum protein binding of APAP, while AMAPS had little effect. The distribution volume of unbound APAP was anomalously increased by APAPS, while it was not affected by AOAPS or AMAPS. Tissue-to-plasma concentration ratios of APAP were significantly increased by APAPS in the liver, kidney and brain, while they were only slightly increased by AOAPS. It was suggested that APAPS has not only the displacing activity of serum protein binding but also other specific effectiveness on the distribution of APAP.
Asunto(s)
Acetaminofén/análogos & derivados , Acetaminofén/farmacocinética , Analgésicos no Narcóticos/farmacocinética , Ésteres del Ácido Sulfúrico/farmacología , Acetaminofén/sangre , Acetaminofén/metabolismo , Acetaminofén/farmacología , Analgésicos no Narcóticos/sangre , Analgésicos no Narcóticos/metabolismo , Animales , Unión Competitiva , Proteínas Sanguíneas/metabolismo , Interacciones Farmacológicas , Isomerismo , Masculino , Ratas , Ratas Wistar , Relación Estructura-Actividad , Ésteres del Ácido Sulfúrico/sangreRESUMEN
A new method based on gastrointestinal transit kinetics has been developed for estimation of the absorption profiles of drugs administered orally as aqueous solutions. The utility of the method was evaluated in rats. The gastrointestinal transit profile for each segment was estimated by in-vivo studies using phenol red, an unabsorbable marker. The gastrointestinal transit profile of phenol red was well explained by a linear gastrointestinal transit kinetic model with eight segments. We also introduced the absorption process into the gastrointestinal transit kinetic model and the plasma profile was predicted by the convolution method. The absorbability of drugs in each segment was assessed by an in-situ absorption study. The validity of the model was evaluated for model drugs with different absorption characteristics. The plasma profiles predicted for ampicillin, theophylline and cephalexin were in good agreement with those observed. The overestimated plasma profile of propranolol suggests that the low bioavailability of propranolol is a result of first-pass metabolism by the intestine wall and the liver, because the calculated absolute absorption is almost perfect. This proposed model is also suitable for estimation of segmental absorption, which is useful for the development of drug delivery systems. We have demonstrated that the plasma profile of orally administered drugs can be predicted by use of gastrointestinal transit and segmental absorbability information and that this method is especially useful for estimating separately the effect of absolute absorption and first-pass metabolism on the bioavailability of drugs.
Asunto(s)
Tránsito Gastrointestinal/fisiología , Absorción Intestinal/fisiología , Farmacocinética , Administración Oral , Ampicilina/administración & dosificación , Ampicilina/sangre , Ampicilina/farmacocinética , Animales , Área Bajo la Curva , Disponibilidad Biológica , Cefalexina/administración & dosificación , Cefalexina/sangre , Cefalexina/farmacocinética , Cefalosporinas/administración & dosificación , Cefalosporinas/sangre , Cefalosporinas/farmacocinética , Cromatografía Líquida de Alta Presión , Masculino , Penicilinas/administración & dosificación , Penicilinas/sangre , Penicilinas/farmacocinética , Fenolsulfonftaleína/química , Propranolol/administración & dosificación , Propranolol/sangre , Propranolol/farmacocinética , Ratas , Ratas Wistar , Teofilina/administración & dosificación , Teofilina/sangre , Teofilina/farmacocinética , Vasodilatadores/administración & dosificación , Vasodilatadores/sangre , Vasodilatadores/farmacocinéticaRESUMEN
The pharmacokinetics of the two-peak plasma profiles of orally administered acetaminophen sulfate (APAPS), a major conjugated metabolite of acetaminophen (APAP), in rats was examined by a two-compartment model having two delivery routes with individual time lags: a direct delivery route of APAPS absorbed in an unchanged form and an indirect one where APAPS was absorbed as APAP after deconjugation in the lower intestine. Pharmacokinetic parameters were estimated by a non-linear least squares program, MULTI(FILT), based on the fast inverse Laplace transform algorithm. Plasma APAPS concentration profiles after oral doses were simulated satisfactorily. In a dose escalation study, the peroral availability of APAPS derived from the direct route was not changed significantly with the doses. However, that from the indirect route was decreased with the dose escalation, suggesting the contribution of a capacity-limited deconjugation of APAPS to APAP by the intestinal microflora to the non-linear pharmacokinetics of orally administered APAPS. The absorption of peroral APAPS in rats at a dose range of 30 to 120 mg APAP eq/kg could be summarized as follows: (1) approximately 25% (22 to 32%) of orally administered APAPS are absorbed from the gastrointestinal tract in an unchanged form; (2) more than 50% (50 to 98%) are deconjugated to APAP in the lower intestinal tract; and (3) the latter plays a significant role as an indirect and non-linear APAPS delivery system because considerable amounts of APAP thus absorbed are rapidly reconjugated to APAPS in the systemic circulation, which gives the second plasma APAPS peak.
Asunto(s)
Acetaminofén/farmacocinética , Analgésicos no Narcóticos/farmacocinética , Acetaminofén/administración & dosificación , Acetaminofén/sangre , Administración Oral , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/sangre , Animales , Cromatografía Líquida de Alta Presión , Colon/metabolismo , Inyecciones Intravenosas , Absorción Intestinal , Masculino , Ratas , Ratas Wistar , Sulfatos/farmacocinéticaRESUMEN
An osteotropic drug delivery system (ODDS) based on a bisphosphonic prodrug has been developed as a novel method for site-specific and controlled delivery of drugs to the bone. The pharmacokinetics and the targeting efficiency of a bisphosphonic prodrug of carboxyfluorescein (CF), disodium (fluorescein-6-carbonyloxy) acetoaminomethylene bisphosphonate (CF-BP), was investigated in rats. After intravenous injection, CF-BP was rapidly taken up into the skeleton, and subsequently cleared from the bone by hydrolysis of its ester linkage at a half-life of 3.2 days. On the other hand, the bone concentration of regenerated CF gradually increased to reach the maximum at 14 days and slowly decreased up to 56 days. Kinetical analysis revealed that bone tissue acts as a reservoir of regenerated CF to supply the parent compound into the systemic circulation. In contrast with CF-BP, CF injected intravenously showed rapid clearance from the plasma and extremely low bone distribution. Therapeutic availability (TA) and drug targeting index (DTI), which were calculated on the basis of the AUCs for CF in the bone and plasma after injection of CF-BP and CF, were 1551 and 6689, respectively. These results suggest that ODDS has a potential to improve not only apparent potency but also therapeutic index of the drugs which exhibit their pharmacological effects in the bone.
Asunto(s)
Huesos/metabolismo , Sistemas de Liberación de Medicamentos , Fluoresceínas/farmacocinética , Organofosfonatos/farmacocinética , Profármacos/farmacocinética , Animales , Área Bajo la Curva , Difosfonatos , Fluoresceínas/metabolismo , Colorantes Fluorescentes/farmacocinética , Inyecciones Intravenosas , Masculino , Organofosfonatos/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
1. To clarify the mechanism of sex-dependent and independent kidney secretion of major nilvadipine metabolites (3, 7) in rat, renal clearance corrected for protein binding and glomerular filtration rate (GFR) was measured in both sexes. The effect of probenecid, an inhibitor of organic anion transport, on these measurements was also investigated. 2. Clear sex-dependent active secretion was observed in the renal excretion of 3 (3-carboxylic acid pyridine derivative). In the female rat, 3, clearance was approximately 32-fold greater than GFR and was markedly decreased by probenecid. Conversely, in the male rat, renal clearance of 3 was only a fraction of GFR and was unaffected by probenecid. 3. Sex-independent active secretion was observed in the renal excretion of 7 (5-carboxylic acid pyridine derivative). In both sexes of rat 7 clearance was about 22-fold greater than GFR and was markedly reduced by probenecid. 4. A clear presence of sex-dependent and independent active secretion mechanisms in the kidney has been demonstrated in rat. The female rat is able to eliminate 3 and 7 in urine by an active secretion mechanism that is inhibited by probenecid. In the male rat, a transport mechanism for 7 is present, but either lacks or is apparently inactive for 3.
Asunto(s)
Antihipertensivos/farmacocinética , Riñón/metabolismo , Nifedipino/análogos & derivados , Caracteres Sexuales , Animales , Bilis/química , Proteínas Sanguíneas/metabolismo , Femenino , Tasa de Filtración Glomerular , Masculino , Tasa de Depuración Metabólica , Nifedipino/metabolismo , Nifedipino/farmacocinética , Potenciometría , Probenecid/sangre , Probenecid/farmacología , Unión Proteica , Ratas , Ratas Sprague-DawleyRESUMEN
The interaction of renal clearance between nilvadipine metabolites, M3 and M7, in male and female rats including protein binding and renal excretion was investigated to clarify the mechanisms involved. In male rats, active renal secretion of M7 (the 5-carboxylic acid pyridine derivative) was reduced in inverse proportion to the molar ratio of the plasma concentration M3/M7 after an i.v. dose of M3 (the 3-carboxylic acid pyridine derivative), and the dosed M3 was excreted only by glomerular filtration. In female rats, the active renal secretion of M7 was unaffected after an i.v. dose of M3, and the dosed M3 was excreted by active secretion. These results indicate an interference of the active secretion of M7 in male rats by M3 on competitive interaction at the renal tubular secretion, even though M3 was excreted only via a filtration process. Female rats may have two distinct and separate active renal secretion mechanisms for M7 and M3, even though these carboxylic acid compounds were eliminated by active transport in the kidney.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacocinética , Riñón/metabolismo , Nifedipino/análogos & derivados , Caracteres Sexuales , Animales , Transporte Biológico Activo , Bloqueadores de los Canales de Calcio/metabolismo , Interacciones Farmacológicas , Femenino , Tasa de Filtración Glomerular , Infusiones Intravenosas , Inyecciones Intravenosas , Túbulos Renales/metabolismo , Masculino , Nifedipino/metabolismo , Nifedipino/farmacocinética , Unión Proteica , Ratas , Ratas Sprague-DawleyRESUMEN
The pharmacokinetics of droloxifene have been studied in female mice, rats, monkeys, and premenopausal and postmenopausal patients. Droloxifene was rapidly and almost completely absorbed after oral dosing. The bioavailability was 8% in mice, 18% in rats and 11% in monkeys due to extensive first-pass metabolism. Droloxifene is widely distributed as demonstrated by its large volume of distribution and the fact that radioactivity in most tissues and organs was higher than in the blood. After oral dosing, the serum and plasma concentrations of unchanged drug declined with terminal half-lives of 1.6 h in mice, 4.3 h in rats, 10.6 h in monkeys and 25 h in patients. The systemic clearance was in the order of mice > rats > monkeys, and nearly equalled the hepatic blood flow in each species. Most of the 14C from [14C]-droloxifene administered orally and i.v. to rats and monkeys was excreted in the faeces. Droloxifene was metabolized extensively by phase I and phase II metabolism. 3-methoxy-4-hydroxy droloxifene was the major metabolite in rat faeces. The metabolites in rat and monkey faeces were not so different qualitatively. Pharmacokinetic parameters were not significantly different between premenopausal and postmenopausal patients.
Asunto(s)
Antagonistas de Estrógenos/farmacocinética , Menopausia/fisiología , Tamoxifeno/análogos & derivados , Adulto , Anciano , Animales , Autorradiografía , Disponibilidad Biológica , Biotransformación , Cromatografía Líquida de Alta Presión , Heces/química , Femenino , Humanos , Inyecciones Intravenosas , Macaca mulatta , Ratones , Ratones Endogámicos BALB C , Persona de Mediana Edad , Ovariectomía , Ratas , Ratas Sprague-Dawley , Tamoxifeno/farmacocinética , Distribución TisularRESUMEN
Acute (approximately 1 week) streptozocin-induced male rats have generally been used as a model for changes in drug metabolism in diabetic humans. The effect of acute (approximately 1 week) and chronic (approximately 3 weeks) streptozocin-induced diabetes on the pharmacokinetics of zenarestat was studied in male and female rats. Total clearance of zenarestat significantly increased in male chronic diabetic rats (15.3-->42.2 ml/hr/kg). In female acute and chronic diabetic rats, pharmacokinetic parameters were similar to those in the control. The fraction unbound to plasma protein was increased with time after streptozocin treatment that was not sex-dependent. In male acute and chronic diabetic rats, the urinary excretion increased compared with the control (acute: 1.7-->7.5%; chronic: 1.9-->13.2% of the dose) after the dose with [14C] zenarestat. It did not change in female acute diabetic rats and decreased in female chronic diabetic rats compared with the control (61.3-->26.2% of the dose). Renal clearance experiments suggested that the decrease in urinary excretion in female chronic diabetic rats is due to a decrease in active secretion. The increase in the urinary excretion in male rats was probably due to a decrease in testosterone levels in the diabetic state.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Diabetes Mellitus Experimental/metabolismo , Quinazolinas/farmacocinética , Enfermedad Aguda , Animales , Proteínas Sanguíneas/metabolismo , Enfermedad Crónica , Diabetes Mellitus Experimental/fisiopatología , Heces/química , Femenino , Tasa de Filtración Glomerular , Masculino , Estructura Molecular , Quinazolinas/sangre , Quinazolinas/orina , Ratas , EstreptozocinaRESUMEN
1. The absorption, distribution and excretion of zenarestat have been studied in male rats and dogs after i.v. and oral administration of 14C-zenarestat. 2. The bioavailability of zenarestat was 93% in rats and 65% in dogs. A major proportion of the plasma 14C in rats and dogs was due to unchanged drug. The terminal elimination half-life of zenarestat in plasma was 6 h in rats and dogs. 3. Except for organs associated with absorption and elimination, tissue 14C levels were lower than plasma levels in rats. The distribution to, and elimination from sciatic nerve were slower than those of other tissues. 4. Most of the 14C from 14C-zenarestat administered orally and i.v. to rats and dogs was excreted in the faeces. After i.v. dosing to bile duct-cannulated rats, 96% of the radioactive dose was excreted in the bile.
Asunto(s)
Aldehído Reductasa/antagonistas & inhibidores , Quinazolinas/farmacocinética , Absorción , Animales , Bilis/metabolismo , Disponibilidad Biológica , Proteínas Sanguíneas/metabolismo , Perros , Heces , Semivida , Masculino , Quinazolinas/sangre , Ratas , Ratas Endogámicas , Especificidad de la Especie , Distribución TisularRESUMEN
The presence of cervical spine instability with respect to preoperative and postoperative changes in angular, horizontal, and rotational displacement of the vertebral body were studied. With the anterior approach, the instability in the remaining unfused segments, and their relation to the kyphotic or lordotic fused segment were studied. With the posterior approach, postoperative ROM (range of motion) could be better maintained, and horizontal displacement was improved in more cases by laminoplasty compared with laminectomy. With the anterior approach, the compensatory function for the loss of motion of the segments resulting from fusion was most remarkable at the levels of C2-3 and C6-7. In the alignment of the anterior fused segments, it appears important that the physiologic lordotic position be maintained.