Plasma disposition

Figure 8. Plasma disposition of sulfadimidine (SDM), its 6-methylhydroxy (CH2OH), 5-hydroxy (SOH) and N -acetyl (N ) metabolites in plasma of a laying-hen during and after cessation of multiple oral dosing of 100 mg SDM/kg/day during 5 days ...

Laying-hens eliminate sulfadimidine rapidly by metabolic pathways including hydroxylation and acetylation. Following intravenous SDM administration, a biphasic elimination-time curve was noticed 10.2 + 3.3 H). Figure 8 shows the plasma disposition of SDM and its metabolites following an oral SDM bolus administration once daily of 100 mg/kg to a chicken. The percentage of N -SDM in plasma is the highest (Table I). Within 3 days of termination of the SDM therapy, plasma concentrations of SDM and its metabolites falls rapidly below the detection limit of the HPLC method (0.02 /ig/ml). 

Lanusse, C. Lifschitz, A. Virkel, G. Alvarez, L. Sanchez, S. Sutra, J.F. Galtier, P. Alvinerie, M. Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle. J. Vet. Pharmacol. Ther. 1997, 20, 91-99. 

Vedaprofen is a propionic acid derivative that, like carprofen and ketoprofen, exists as two enantiomers with different pharmacokinetic profiles in the horse. For example, the plasma disposition of S(-t-)-vedaprofen is characterized by a very rapid decline with a plasma half-life of less than 1 h while R(-)-vedaprofen has a more prolonged elimination phase with a plasma half-life of over 2h (Lees et al 1999). Both enantiomers also accumulate in and exhibit a delayed elimination from inflammatory exudates. In horses, vedaprofen appears to be slightly selective for the COXl enzyme. For example, the median effective concentration for inhibition of serum TXB2 production, which is assumed to be a reflection of COXl activity, was much lower than that for inhibition of inflammatory infiltrate PGE2 production, which is assumed to be a reflection of COX2 activity. Although the results of these studies are promising, there are no published data on the clinical effectiveness and safety of vedaprofen in horses. 

Matsumoto S, Arase Y, Takakura Y, et al. Plasma disposition and in vivo and in vitro antitumor activities of mitomycin C-dextran conjugate in relation to the mode of action. Chem Pharm Bull 1985 33 2941-2947. 

Figure 2. Effect of antivenom administration on plasma disposition of Vipera aspis venom in experimentally envenomed rabbits. Five rabbits were intramuscularly injected with 700 pg.kg of I-labelled Vipera aspis venom. Seven hours later, they were intravenously injected with 2.5 ml of Ipser Europe serum diluted with 2.5 ml of saline. Plasma samples were analyzed by ELISA for their content in free antigens (O) and by counting radioactivity for their total concentration of antigens ( ).

Figure 46-5 shows a variety of ways in which proteins are distributed in the plasma membrane, in particular, the amino terminals of certain proteins (eg, the LDL receptor) can be seen to be on the extracytoplasmic face, whereas for other proteins (eg, the asialoglycoprotein receptor) the carboxyl terminals are on this face. To explain these dispositions, one must consider the initial biosynthetic events at the ER membrane. The LDL receptor enters the ER membrane in a manner analogous to a secretory protein (Figure 46-4) it partly traverses... 

Age does not significantly affect plasma concentrations or disposition of ibuprofen however, investigators have determined that the onset of antipyresis and maximum antipyretic effect is greater in children less than one year old as compared to children older than 6 years [43]. The authors hypothesized that this accelerated response was related to the greater relative body surface area of the young child. It should be noted that cystic fibrosis patients do have a higher clearance of ibuprofen [43a]. 

Unchanged passive diffusion and no change in bioavailability for most drugs l Active transport and i bioavailability for some drugs l First-pass extraction and T bioavailability for some drugs i Volume of distribution and T plasma concentration of water-soluble drugs T Volume of distribution and T terminal disposition half-life (t ) for fat-soluble drugs... 

Attempts to gather evidence that both phenol red and its glucuronide are excreted by saturable transfer processes were made by measuring drug disposition at four different doses of phenol red. Of the four doses studied (j3) only the two extreme doses are shown in Table III. Over this range of doses, there was no evidence of saturation in terms of concentration, of either the plasma or kidney. There was no proportionality between... 

Table V contains data for two model substances, p-aminohippurate (PAH) and phenol red. Consideration of the highest values in this table tells you where the major portions of the substances appear. For example, urine and bile show the largest concentrations of PAH and phenol red. Both compounds appear in significant concentrations in the kidney while the values in muscle, brain and cerebrospinal fluid (CSF) are invariably lower than the values seen in plasma. The values in parentheses (Table V) are percent of the administered dose in a given tissue or fluid compartment. They add to the previous information by revealing the overall importance of a particular compartment in the disposition of a substance. For example, while the hepatic concentrations of PAH and phenol red at 4 hrs. are only about 2-fold those of plasma, the large size of the shark liver relative to its body weight, typically about 10%, leads to the appearance of 30-40% of these substances in the liver. The relative handling of these compounds by the urinary and biliary system is obvious from considering the percentage figures. Thus in 24 hours phenol red is about equally distributed in the bile and urine (38 vs 31%) the urinary route is the dominant route of excretion of PAH, i.e., 56 vs 2%.

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