Renal distribution

Pharmacokinetic Aspects of Antisense Oligodeoxynucleotides and Renal Distribution... 

Transport of solutes and water occurs both across and between the epithelial cells that line the renal tubules. Transport is both active (energy requiring) and passive, but many of the so-called passive transport processes are dependent upon or secondary to active transport processes, particularly those involving sodium transport. All known transport processes involve receptor or mediator molecules, many of which have now been identified and characterized using molecular biological teclmiques. The activity of many of these molecules is regulated by phosphorylation facilitated by protein kinase C or Their renal distribution has... 

The recommended dose of pemetrexed is 500 mg/m2 administered as an intravenous infusion over 10 min on Day 1 of each 21-day cycle. Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated in the urine, with 70-90% of the dose recovered unchanged within the first 24 h following administration. Pemetrexed has a steady-state volume of distribution of 16.1 L. Pemetrexed is highly bound (approximately 81%) to plasma proteins. Binding is not affected by the degree of renal impairment. Plasma... 

This complex contains 11 polypeptide subunits of which only one is encoded by mtDNA. Defects of complex III are relatively uncommon and clinical presentations vary. Fatal infantile encephalomyopathies have been described in which severe neonatal lactic acidosis and hypotonia are present along with generalized amino aciduria, a Fanconi syndrome of renal insufficiency and eventual coma and death. Muscle biopsy findings may be uninformative since abnormal mitochondrial distribution is not seen, i.e., there are no ragged-red fibers. Other patients present with pure myopathy in later life and the existence of tissue-specific subunits in complex III has been suggested since one of these patients was shown to have normal complex 111 activity in lymphocytes and fibroblasts. 

Utilization of F-2DFM instead of F-2DFG for the PET method was examined. A similar or indistinguishable level of uptake of both compounds in brain (human and rats) and heart (rats) was shown, as well as of renal excretion (rats). Also, almost the same distribution of both compounds was shown in rat and rabbit tumors. 

Next, Reilly et al. [65] localized the Na /H exchanger gene product in renal epithelial cells where the distributions of the kinetic isoforms was well-established. The strategy was based on the observation that the resistant- and sensitive-types are restricted to the apical and basolateral membranes, respectively, in confluent LLC-PK]/Clone 4 cells [8]. Thus, if proteins encoded by the cloned cDNAs localized to the apical membrane this would indicate that they represent the resistant-type. Localization to the basolateral membrane would prove they were the sensitive-type and presence on both membranes would suggest that the two functional isoforms had identical primary structures. Na exchanger proteins were localized by... 

Clearance is defined as the fraction of the volume of distribution Vp that is cleared of the drug per unit of time. In the case of elimination from the kidneys, the clearance provides a measure for the effectiveness of renal elimination with respect to the dmg under study. 

The area under the PCP concentration-time curve (AUC) from the time of antibody administration to the last measured concentration (Cn) was determined by the trapezoidal rule. The remaining area from Cn to time infinity was calculated by dividing Cn by the terminal elimination rate constant. By using dose, AUC, and the terminal elimination rate constant, we were able to calculate the terminal elimination half-life, systemic clearance, and the volume of distribution. Renal clearance was determined from the total amount of PCP appearing in the urine, divided by AUC. Unbound clearances were calculated based on unbound concentrations of PCP. The control values are from studies performed in our laboratory on dogs administered similar radioactive doses (i.e., 2.4 to 6.5 pg of PCP) (Woodworth et al., in press). Only one of the dogs (dog C) was used in both studies. 

CF patients have larger volumes of distribution of many antibiotics due to an increased ratio of lean body mass to total body mass and lower fat stores. CF patients also have an enhanced total body clearance, although the exact mechanism has not been determined. Increased renal clearance, increased glomerular filtration rate, decreased protein binding, increased tubular secretion, decreased tubular reabsorption, extrarenal elimination, and increased metabolism have all been proposed as possible reasons for the increased clearance. 

Although most CF patients have shorter half-lives and larger volumes of distribution than non-CF patients, some patients exhibit decreased clearance. Possible causes include concomitant use of nephrotoxic medications, presence of diabetic nephropathy, history of transplantation (with immunosuppressant use and/or procedural hypoxic injury), and age-related decline in renal function in older adult patients. Additionally, CF patients are repeatedly exposed to multiple courses of IV aminoglycosides, which can result in decreased renal function. Evaluation of previous pharmacokinetic parameters and trends, along with incorporation of new health information, is key to providing appropriate dosage recommendations. 

Gabapentin Modulate calcium channels and enhance GABA activity Loading dose Not recommended due to short half-life Maintenance dose 900-3600 mg/day in 3-4 divided doses (doses up to 1 0,000 mg/day have been tolerated) Half-life Not established 5-7 hours (proportional to creatinine clearance) Apparent volume of distribution 0.6-0.8 L/kg Protein binding less than 10% Primary elimination route Renal Drowsiness, sedation Peripheral edema, weight gain... 

Levetiracetam Unknown Loading dose Not recommended due to excessive adverse effects Maintenance dose 1 000-3000 mg/day. Start at 1 000 mg/day and titrate upward as indicated by response Half-life Not established 6-8 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding less than 10% Primary elimination route 70% renal 30% hepatic Somnolence, dizziness Depression... 

Pharmacodynamics Duration 1-4 weeks Absorption IM slow Time to peak serum levels 12-24 hours Duration 15-24 hours Absorption IM slow Distribution Poor blood-brain barrier penetration, enters breast milk Metabolism =30% hepatic inactivation Protein binding 65% Time to peak serum levels 1-4 hours Excretion Urine (60-90% as unchanged drug) Clearance Renal... 

Zalcitabine (ddC) Hivid (anticipated discontinuation of distribution in 2006) 0.375-, 0.75-mg tab 0.75 mg tid CrCI Dose (mL/minute) 10-40 0.75 mg bid less than 10 0.75 mg qday No data on hemodialysis None Peripheral neuropathy stomatitis, lactic acidosis with hepatic steatosis (rare but potentially life-threatening toxicity with use of NRTIs) pancreatitis Renal excretion... 

Electrolytes are involved in many metabolic and homeostatic functions, including enzymatic and biochemical reactions, maintenance of cell membrane structure and function, neurotransmission, hormone function, muscle contraction, cardiovascular function, bone composition, and fluid homeostasis. The causes of electrolyte abnormalities in patients receiving PN may be multifactorial, including altered absorption and distribution excessive or inadequate intake altered hormonal, neurologic, and homeostatic mechanisms altered excretion via gastrointestinal and renal losses changes in fluid status and fluid shifts and medications. 

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