Distribution in tissue

In contrast to many chemotherapeutic agents in cancer therapy, boron compounds for BNCT do not require a tumoricidal action in their own right. For their successful application in the therapy of patients, it is important to deliver, to the tumor, a radiation dose which is higher than the radiation dose to the surrounding tissue. The demonstration that this is actually achieved lies ultimately in the treatment of the tumor in question. Because of the short range of the particles produced in the 10B(n,a)7Li reaction, it is very important where, on a cellular and subcellular dimension, the neutron capture reaction takes place. Different methods for boron detection and quantification give different resolution of the boron distribution. It is instructive to compare these methods, both for their precision and lower detection limits, as well as for their ability to yield an image of the boron distribution in tissue (Table 2.2-1). 

Acid phosphatase is widely distributed in tissues. Male prostate glands7 are extraordinarily rich, and this enzyme is implicated in the physiology of sex. Men excrete in the urine about 3.5 times as much... 

Hexokinase/glucokinase glucose entering the cell is trapped by phosphorylation using ATP. Hexokinase is widely distributed in tissues, whereas glucoldnase is found only in hepatocytes and pancreatic 3-islet cells. Table I-I2-2 identifies the differences in their... 

Absorption/Distribution - The TCAs are well absorbed from the Gl tract with peak plasma concentrations occurring in 2 to 4 hours they undergo a significant first-pass effect. They are highly bound (more than 90%) to plasma proteins, are lipid soluble and are widely distributed in tissues, including the CNS. 

They are well absorbed after oral administration with a bioavailability of 70-80%. They have a rather low protein binding, 20 0%, and are widely distributed in tissues, body fluids and bone. They are eliminated mainly by glomerular filtration and tubular secretion with a half-life of 3-7 hours. Up to 40% of the dose is metabolized by the liver. 

Pharmacokinetics Parenteral Widely distributed in tissues. Metabolized in liver. Primarily excreted in urine. Half-life 24 hr. Topical No systemic absorption following application to intact skin. Intravaginally Small amount absorbed systemically. 

It is poorly absorbed from GIT and topically. After IV administration it is widely distributed in tissues. About 60% drug is metabolized in liver and excretion occurs slowly both in urine and bile. 

After administration it is rapidly absorbed and distributed in tissue e.g. liver, intestine and kidneys. It is metabolised in liver and converted to active metabolite dihydroartemisinin. 

Tubercle bacilli are usually inhibited in vitro by aminosalicylic acid, 1-5 mcg/mL. Aminosalicylic acid is readily absorbed from the gastrointestinal tract. Serum levels are 50 mcg/mL or more after a 4-g oral dose. The dosage is 8-12 g/d orally for adults and 300 mg/kg/d for children. The drug is widely distributed in tissues and body fluids except the cerebrospinal fluid. Aminosalicylic acid is rapidly excreted in the urine, in part as active aminosalicylic acid and in part as the acetylated compound and other metabolic products. Very high concentrations of aminosalicylic acid are reached in the urine, which can result in crystalluria. 

Metronidazole is a nitroimidazole antiprotozoal drug (see Chapter 52) that also has potent antibacterial activity against anaerobes, including bacteroides and Clostridium species. It is well absorbed after oral administration, is widely distributed in tissues, and reaches serum levels of 4-6 mcg/mL after a 250-mg oral dose. Metronidazole can also be given intravenously or by rectal suppository. The drug penetrates well into the cerebrospinal fluid and brain, reaching levels similar to those in serum. Metronidazole is metabolized in the liver and may accumulate in hepatic insufficiency. 

Mefloquine hydrochloride is a synthetic 4-quinoline methanol that is chemically related to quinine. It can only be given orally because severe local irritation occurs with parenteral use. It is well absorbed, and peak plasma concentrations are reached in about 18 hours. Mefloquine is highly protein-bound, extensively distributed in tissues, and eliminated slowly, allowing a single-... 

Spiramycin is incompletely absorbed from the gastrointestinal tract, but widely distributed in tissues. After absorption, some portion of the drug is desmy-carosylated into neospiramycin by gastric acid neospiramycin does not differ from the parent drug in the antibacterial activity (109). Spiramycin is metabolized in the liver to active metabolites and excreted in bile but also in urine. It is found in breast milk. In raw milk, the neospiramycin level was 6-7% of the spiramycin content (110). 

Studies in pigs treated intramuscularly with enrofloxacin at a dosage of 2.5 mg/kg bw for 3 days showed that the parent compound was absorbed and efficiently distributed in tissues the concentrations of enrofloxacin detected in muscle, liver, kidney, and fat tissues at 10 days after treatment were 15, 26, 20, and... 

From residue data with pigs, poultry, and cattle after oral administration, and with cattle after intravenous administration, it appears that the distribution profde of doxycycline in these animals is roughly comparable to that of oxytetracycline. Highest residue concentrations are found in kidney, followed by liver, skin, fat, and muscle. Tissue depletion studies in pigs treated intramuscularly with doxycycline at a 10 mg/kg bw dose for 4 days showed that the parent compound was absorbed and efficiently distributed in tissues (252). The concentrations of doxycycline detected in lung, muscle, liver, and kidney tissues at day 6 after treatment were 0.067, 0.047, 0.18, and 0.47 ppb, respectively detectable doxycycline residues were not present in fat at that withdrawal time. 

After oral application, bacitracin is hardly absorbed by the gastrointestinal tract and, therefore, its distribution in tissues is considered negligible (6). Approximately 95% of an orally administered dose is excreted via feces, and only 3% or less via urine. Bacitracin is primarily metabolized to desamidobacitracin and further to smaller peptides and amino acids. Main metabolites identified in feces are bacitracin A, Bi, B2, F, desamidobacitracin, and catabolic peptides. In urine and bile, only hydrolytic cleavage products such as small peptides are present. 

G Varela-Moreiras, E Seyoum, J Selhub. Combined affinity and ion pair liquid chromatographies for the analysis of folate distribution in tissues. J Nutr Biochem 2 44-53, 1991. 

C-B is a synthetically produced hallucinogen that is most closely related to mescaline. It acts primarily on the central serotonin receptors of the brain. Serotonin is a chemical derived from the amino acid tryptophan, and widely distributed in tissues. It acts as a neurotransmitter, constricts blood vessels at injury sites, and may affect emotional states. 2C-B works by interfering with serotonin in the brain. 

Anghileri LJ, Maincent P, Thouvenot P. 1994. Long-term oral administration of aluminum in mice. Aluminum distribution in tissues and effects on calcium metabolism. Ann Clin Lab Sci 24 22-26. 

Fletcher GL. 1974. The dynamics of yellow phosphorus in Atlantic cod and Atlantic salmon Biological half-times, uptake rates and distribution in tissues. Environ Physio Biochem 4 121-138. 

Manuilov, K. K. Use of a physiologically-based pharmacokinetics model for analysis of antibiotic distribution in tissue. Int J Clin Pharmacol Ther Toxicol 1992, 30 548-549. 

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