Elimination renal

Renal metabolism of peptides and small proteins is mediated through three highly effective processes (Fig. 2.4). Consequently, only minuscule amounts of intact protein are detectable in the urine. 

The first mechanism involves the glomerular filtration of larger, complex peptides and proteins, followed by reabsorption into endocytic vesicles in the proximal tubule and subsequent hydrolysis into small peptide fragments and amino acids [76]. This mechanism of elimination has been described for IL-2 [77], IL-11 [78], growth hormone [79], and insulin [80]. 

The second mechanism entails glomerular filtration followed by intraluminal metabolism, predominantly by exopeptidases in the luminal bmsh border membrane of the proximal tubules. The resulting peptide fragments and amino acids 

The third mechanism is peritubular extraction of peptides and proteins from postglomerular capillaries and intracellular metabolism. Experiments using iodi-nated growth hormone (125I-rGH) have demonstrated that, while reabsorption into endocytic vesicles at the proximal tubule is still the dominant route of disposition, a small percentage of the hormone may be extracted from the peritubular capillaries [79, 86]. Peritubular transport of proteins and peptides from the baso-lateral membrane has also been shown for insulin [87] and the mycotoxin ochra-toxin A [88]. 

Growing hair can serve as a limited route through which chemicals can escape the body. Pollutants such as mercury and drugs such as cocaine have been measured in human hair, and hair analyses is often used as a marker of exposure to such materials. 

The kidneys are the sites of elimination of water-soluble chemicals that are removed from the blood by the process of reverse filtration. Two characteristics are primarily responsible for determining whether a chemical will be eliminated by the kidneys size and water solubility. 

The reverse filtration process requires that chemicals to be removed from the blood are able to pass through 70 to 100 A pores. As a rule, chemicals having a molecular mass of less than 65,000 are sufficiently small to be subject to reverse filtration. 

Water Solubility. Non-water-soluble chemicals will be transported to the kidneys in association with transport proteins. Thus, in association with these proteins, the chemicals will not be able to pass through the pores during reverse filtration. Lipophilic chemicals are generally subject to renal elimination after they 

Blood is delivered to the human kidney by the renal artery. Blood flows to the kidneys of the adult human at a rate of roughly 1 L/min. The adult human kidney contains approximately 1 million functional units, called nephrons, to which the blood is delivered for removal of solutes. Collected materials are excreted from the body in the urine. 

In older children, significant absorption above normal expectations is likely only when large areas of skin are damaged or inflamed. Examples inclnde children with significant burns, psoriasis or eczema. 

Enhanced percutaneous absorption may offer a possible route of administration for some drugs, although more research is needed. 

When preparations are applied to the skin of infants, particularly preterm neonates, the potential for systemic absorption of excipients as well as any active drug should always be considered. 

Developmental changes in renal function, particularly glomerular filtration and active tubular secretion, affect the renal excretion of many drugs. In the preterm neonate the kidney is still undergoing development or nephrogenesis. Renal function at birth, and how it develops after birth, are related to the maturity of the developing nephrons. 

In neonates over 1.5 kg glomerular filtration rate (GER) increases dramatically in the first 2 weeks following birth due to adaptive changes in renal blood flow and the recruitment of mature, functioning nephrons. In term neonates the GFR is approximately 2—4 mL/min per 

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Oral formulations of metformin are rapidly and completely absorbed. The agent is poorly bound to plasma proteins its duration of action is determined exclusively by renal elimination. Higher concentrations of metformin than in most tissues are found in the intestinal mucosa, giving tise to common side effects (irritation, diarrhoea etc.). 

The primary urinary metabolites of trichloroethylene in humans are trichloroethanol, trichloroethanol glucuronide, and TCA (Monster et al. 1979 Nomiyama and Nomiyama 1971 Sato et al. 1977). The halftime for renal elimination of trichloroethanol and trichloroethanol glucuronide has been determined in several studies to be approximately 10 hours following trichloroethylene exposure (Monster et al. 1979 Sato et al. 1977). The urinary excretion of TCA is much slower, and data from several studies indicate that the halftime of urinary TCA is approximately 52 hours because the metabolite is very tightly and extensively bound to plasma proteins (Monster et al. 1976 Sato et al. 1977). 

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. 

Fondaparinux has been used for the treatment of DVT and PE in two large Phase III trials and is approved by the FDA for these indications. Fondaparinux is as safe and effective as IV UFH for the treatment of PE and SC LMWH for DVT treatment.36,40 The recommended dose for fondaparinux in the treatment of VTE is based on the patient s weight (Table 7-3). Fondaparinux is renally eliminated and accumulation can occur in patients with renal dysfunction. Due to the lack of specific dosing guidelines, fondaparinux is contraindicated in patients with severe renal impairment (CrCl less than 30 mL/minute). Baseline renal function should be measured and monitored closely during the course... 

Primarily renal elimination of unchanged drug Would not expect hepatic impairment to have an effect (no data) Expect sign, effect of renal impairment and no effect of advanced age (beyond decreased CrCI with age) (no data)... 

Treatment fluconazole, itraconazole, ketoconazole, Amphotericin B Consider liposomal products decrease or stop CSA or TAC to minimize nephrotoxicity Remember to adjust doses of renally eliminated drugs (e.g., acyclovir, ganciclovir, TMP-SMX)... 

Renal and/or hepatic function should be considered in every patient prior to initiation of antimicrobial therapy. In general, most antimicrobials undergo renal elimination and... 

Renal insufficiency Decrease of renal elimination, leading to increased efficacy of warfarin... 

Calcium Adequate intake (Table 3-1) in divided doses Absorption-predominantly active transport with some passive diffusion, fractional absorption 10-60%, fecal elimination for the unabsorbed and renal elimination for the absorbed calcium... 

D 2,800 or 5,600 units, or 75 mL liquid weekly renal elimination (of absorbed)... 

Renal elimination 3% nasal availability 95% bioavailability Tmax -50 minutes T1/2 60 minutes Hepatic metabolism 10% gel absorption (5 mg absorbed from 50 rug testosterone in 5 g of gel)... 

Acetohexamide (Y) Dymelor 250, 500 250 125-250 500 1,500 Up to 16 hours Metabolized in liver metabolite potency equal to parent compound renally eliminated... 

Nateglinide (N) Starlix 60, 120 120 with meals 120 with meals NA 120 mg three times a day Up to 4 hours Metabolized by cytochrome P450 (CYP450) 2C9 and 3A4to weakly active metabolites renally eliminated... 

Renal elimination of unchanged drug accounts for 66% of drug clearance, and the dose should be adjusted for impaired renal function. The role of therapeutic drag monitoring is unknown. It has linear pharmacokinetics and is metabolized in blood by nonhepatic enzymatic hydrolysis. 

Cancer and hyperparathyroidism are the most common causes of hypercalcemia. The primary mechanisms are increased bone resorption, increased GI absorption, and decreased renal elimination. 

T or si Free fraction of highly plasma protein-bound drugs si Clearance and T t1/2 for some oxidatively metabolized drugs si Clearance and T t1/2 for drugs with high hepatic extraction ratios si Clearance and T t 2 for renally eliminated drugs and active metabolites... 

EBM (3), inappropriate drugs (4), correct dose (2), food interactions (8), personalised medicine (10), renal elimination (2), common conditions (5), neuro-psychiatric disorders (6)... 

Bendayan R, SuUivan JT, Shaw C, Erecker RC, Sellers EM (1990) Effect of cimetidine and ranitidine on the hepatic and renal elimination of nicotine in humans. Eur J Chn Pharmacol 38(2) 165-169... 

Several other modifications have been explored for the targeted delivery of SOD. Chemical modification with hydrophilic monomethoxypolyethyleneglycol polymers (MPEG) resulted in a derivative with an increased molecular weight of 130 kDa, and hence a reduced renal elimination rate. The MPEG-SOD preparations reduced arthritic lesions in a complete adjuvant arthritis model in the rat, while native SOD did not show an anti-inflammatory effect [55]. 

In the case of drugs renally eliminated in unchanged form, the half-life of elimination can be calculated from the cumulative excretion in urine the final total amount eliminated corresponds to the amount absorbed. 

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