Plasma profile

FIGURE 10 Plasma profile of nafarelin acetate and biological response parameter in female Rhesus monkeys after injection with 100 mg of 55 45 lactide/glycolide microspheres. (From Ref. 118.)... 

Figure 9 Plasma profile of L-a-methyldopa following intravenous dose of L-a-methyl-dopa and jejunal dose of L-a-methyldopa-phenylalanine and L-a-methyldopa (n = 6-7). ( ) L-a-methyldopa following jejunal dose of prodrug (V) L-a-methyldopa jejunal dose ( ) L-a-methyldopa intravenous dose.

Some idea of the rate of absorption can be obtained from examination of the plasma concentration-time profile. It should be remembered, however, that the time to maximum plasma concentration Y ) is not when absorption is complete but when the rates of drug absorption and elimination are equal. Thus two drugs with the same absorption rate will differ in /max if elimination rates differ. Assessment of the rate of absorption can also be confounded by complex or slow drug distribution. For example, the calcium-channel blocker amlodipine has a much later /max than other similar drugs. This is not due to slow absorption but to partitioning in the liver membrane with slow redistribution. A quantitative assessment of the rate of absorption can be obtained by deconvolution of plasma profiles following IV and oral administration. 

Nicolaides E, Symillides M, Dressman JB, Reppas C. Biorelevant dissolution testing to predict the plasma profile of highly lipophilic drugs after oral administration. Pharm Res 2001 18(3) 380-388. 

Charman W, Rogge M, Boddy A, Barr W, Berger B. Absorption of danazol after administration to different sites of the gastrointestinal tract and the relationship to single- and double-peak phenomena in the plasma profiles. J Clin Pharmacol 1994 33 1207-1212. 

In the study by Parrott et al. [7], a generic PBPK model was applied to predict plasma profiles after intravenous and oral dosing to the rat for a set of 68 compounds from six different chemical classes. The compounds were selected without particular bias and so are considered representative of current Roche discovery compounds. The physicochemical properties of the compounds are rather different from those of marketed compounds in particular they have higher lipophilicity (mean logP = 4) and lower aqueous solubility as well as a tendency to be neutral at physiological pH. The more extreme property values can present experimental determination challenges and so for consistency all predictions were made on the basis of calculated lipophilicity and protein binding while in vitro... 

Solanky, K.S. et al., Application of biofluid IH nuclear magnetic resonance-based metabonomic techniques for the analysis of the biochemical effects of dietary isoflavones on human plasma profile. Anal. Biochem., 323, 197, 2003. 

Preliminary in vivo experiments carried out on this biphasic pulsed release device containing ibuprofen as a model drug reveal two distinct peaks in plasma profiles, thus indicating that the in vitro results are in good agreement with the in vivo blood levels. 

Fig. 4 shows the plasma profiles obtained after oral administration of two plain tablets of 300 mg of ibuprofen prepared with two different batches of active principle, having differing particle size distributions dv= 1.5 pm and 5 pm), compared with a conventional marketed ibuprofen tablet. The plasma levels are strongly dependent on the specific surface area of the ibuprofen powder. 

The elimination process is represented by the elimination rate constant ke, which may be determined from the gradient of the plasma profile (Fig. 3.25). The reasons for the overall process of elimination being first order are that the processes governing it (excretion by various... 

Figure 18 Plasma profiles of inhaled ( AERx ) versus intravenous ( IV ) morphine. Subjects received four inhalations of morphine sulfate (8.8 mg loaded doses) via the AERx system and 4.0 mg morphine sulfate intravenously on separate days. Both dosages were delivered over a 4 min period.

FIGURE 6.2 Probucol plasma profiles following oral administration (100 mg/kg) to rats in three different oily vehicles peanut oil (LCT, ), miglyol (MCT, A), or paraffin oil ( ). (From Palin, K.J. and Wilson, C.G., J. Pharm. Pharmacol., 36, 641, 1984. With permission.)... 

In addition to increased overall bioavailability of lipophilic molecules, lymphatic transport of a drug provides further advantages, including avoidance of hepatic first pass metabolism, a potential to target specific disease states known to spread via the lymphatics, and improved plasma profile of the drug. 

Fig. 11. Effects of aging and caloric restriction on the 24-hour plasma profiles of total and free corticosterone in young (3-7 months of age) and old (21-25 months of age) male F344 rats. Calorically restricted animals were fed just before turning off the light (arrow). The light was off from 17 00 to 05 00 and on from 05 00 to 17 00. Adapted from reference 56.

As stated above, the Vss calculation using Eqs. (5) or (10) is valid only when elimination exclusively occurs from the sampling (plasma/blood) compartment. When some or all elimination occurs from the tissue compartment (Fig. 7.1), the concentration versus time profile will still be characterized by a bi-exponential equation however, the ability of modeling systems to quantify the micro rate constants is lost. That is to say, essentially identical bi-exponential concentration time profiles are possible with and without elimination from the tissue compartment. Therefore, when modeling from a plasma profile only, there is no way of determining if the exit of drug from the body is exclusive to the central compartment. 

An advantage of transdermal delivery in eliminating first-pass metabolism in evident in these comparative studies of the delivery of DIL by intravenous, oral, and topical routes. deAcDIL is the primary metabolite of DIL identified in oral delivery (12, 13). Typical plasma profiles are compared in Figure 4 for oral and topical delivery. 

In a typical setup, insulin is given subcutaneously and absorbed with a given plasma profile and a somewhat delayed interstitial profile. More rarely, insulin is infused to a constant insulin concentration. The interstitial insulin stimulates the... 

Fig. 6.6 Blood plasma profiles of octreotide after peroral administration of 15 mg/pig A, Subject 2 B, Subject 6. Core ( ) core inside ( ) octreotide without any polymer (A) core outside with TMC (x) (Dorkoosh et al. 2002)...

After a drug is administered to the body it goes through various phases of distribution. If we were to make periodic plasma measurements of a drug following its administration, its plasma profile would be a composite of various dynamic processes serving to increase or decrease its concentration. The processes of distribution can be considered in terms of compartments. 

The phase space reconstruction approach, making use only of the hormone plasma profiles, was utilized in order to assess the dimensionality and thus expose the chaotic nature of the underlying dynamics of various hormones. In... 

Fig. 2. Relationship of observed AUQnf values for XYZ1234 plasma-profiles versus dose,with linear regression (bold line), and the 95 % confidence range (dashed line).

The resulting set of 10 equations, assuming toroidal symmetry and replacing the radial component of the ion momentum balance equation by an ad hoc diffusions ansatz (likewise the other radial transport coefficients are replaced by ad hoc anomalous expressions) is the basis for most current edge plasma simulation models. These anomalous ad-hoc coefficients are free model parameters. They, and their empirical scalings, can be determined by comparison with experimental plasma profile data, if one can be sure that all other terms in the equations, and in particular the source terms Sm resulting from atomic and molecular processes, are accurately known and implemented. 

Plumb RS, Johnson KA, Rainville P, Shockcor JP, Williams R, Granger JH, Wilson ID (2006) The detection of phenotypic differences in the metabolic plasma profile of three strains of Zucker rats at 20 weeks of age using ultra-performance liquid chromatog-raphy/orthogonal acceleration time-of-flight mass spectrometry. Rapid Commun. Mass Spectrom. 2006 20 2800-2806. 

Fig. 7 Diagrammatic illustration of the subcutaneous implantation of Norplant implants. The subcutaneous release profile of levonorgestrel in female volunteers for up to 6 years and the resultant plasma profile as compared to those obtained by oral administration. (Adapted from Refs. l)...

Fig. 12 Cross-sectional view of a unit of Deponit system, showing various structural components, and the plasma nitroglycerin concentration profiles in six human volunteers, each receiving 1 unit of Deponit system (16 cm, with a delivery rate of 5mg/day) for 24 h. (Plasma profiles are plotted from data from Ref...

Fig. 7 Plasma profile of norethinedrone following the intravaginal insertion of ethynodiol diacetate-releasing vaginal devices in rabbits for 56 days and after device removal. (From Ref. l.)...

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