Absorption lag time

For drugs that show significant oral bioavailability (e.g., salbutamol [75]), terbutaline sulfate [76], budesonide [77]), different approaches, such as the charcoal-block technique, or the knowledge of differences in the pulmonary and GI absorption lag times can be utilized to determine the pulmonary fate of the inhaled drug. 

The pharmacokinetics of the analgesic drug was described by a two-compartment model, with first-order absorption and absorption lag time. The population parameters of this model are given in Table 25.1. The value of a given parameter P, for subject i, is given by... 

Therefore, full-face phenol-based peel should always be performed under full cardiopulmonary monitoring. The average lag time for the onset of the arrhythmias was 17.5 min from the beginning of the peel, and they are usually not delayed for more than 30 min after the peel. Cardiac arrhythmias are more common while applying the solution on the thin skin of eyelids. In this area skin absorption is maximal therefore, application should be performed extremely cautiously. If arrhythmia occurs, the application of phenol should be stopped until... 

Other applications of the previously described optimization techniques are beginning to appear regularly in the pharmaceutical literature. A literature search in Chemical Abstracts on process optimization in pharmaceuticals yielded 17 articles in the 1990-1993 time-frame. An additional 18 articles were found between 1985 and 1990 for the same narrow subject. This simple literature search indicates a resurgence in the use of optimization techniques in the pharmaceutical industry. In addition, these same techniques have been applied not only to the physical properties of a tablet formulation, but also to the biological properties and the in-vivo performance of the product [30,31]. In addition to the usual tablet properties the authors studied the following pharmacokinetic parameters (a) time of the peak plasma concentration, (b) lag time, (c) absorption rate constant, and (d) elimination rate constant. The graphs in Fig. 15 show that for the drug hydrochlorothiazide, the time of the plasma peak and the absorption rate constant could, indeed, be... 

Commercial samples containing approximately 400 mg of ephedra per capsule yield roughly 5 mg of ephedrine, 1 mg of pseudoephedrine, and less than 1 mg of methylephedrine (White et al. 1997). For a dose of four capsules, yielding approximately 20 mg of ephedrine, the elimination half-life is 5.2 hours. The time to reach maxium concentration is 3.9 hours. Compared to pure ephedrine tablets, the elimination kinetics of ephedra are comparable. However, ephedra showed somewhat different absorption kinetics (e.g., lag time, area under the concentration-time curve, and maximum plasma concentration). So, ephedra tablets may vary from pure ephedrine in the onset of action, but the durations of action are grossly equivalent. 

In summary, the lag time of drug release may be controlled by the rate at which water penetrates through the coating or shell, the rate of fluid absorption of the polymer layer, the osmotic activity of salts and osmopolymers, the erosion and dissolution rate of the polymer layers and the thickness of the layers or coatings. 

In general, it is assumed that the oral absorption process follows Lrst-order kinetics. This assumption appears to be valid for majority of the drugs. The Lrst-order process can also satisfactorily describe the oral absorption process of some drugs with very poor water solubility. Sometimes, the inclusion of the absorption time lag may appear to be needed to account for the lag time for the dissolution of the drug substance from the dosage form into the aqueous media in the Gl tract. 

First-order absorption model with or without lag time... 

Time-dependent absorption using a change-point model with orwithout lag time (Higaki etal.,2001)... 

Simultaneous Lrst- (with and without lag time) and zero-order absorption... 

Of all the absorption models tested, the last absorption model (Lrst-order model where the absorption rate constant and lag time were treated as a mixture model) Ltted the data best. In 97% of the subjects, the population-estimated absorption rate constant was-1 vfifttia lag time of 0.821 h, and in the remaining 3% of the subjects, the population-estimated absorption rate constant was 0.361 h1 without a lag time (Bonate et al., 2004). 

This time controlled release tablet with a designated lag time followed by a rapid release may provide an alternative to site-specific delivery of drugs with optimal absorption windows or colonic delivery of drugs that are sensitive to low pH or enzyme action for the treatment of localized conditions such as ulcerative colitis, Crohn s disease, and irritable bowel syndrome (IBS). Also, by controlling a predetermined lag time of drug from dosage form, the release behavior can be matched with the body s circadian rhythm pattern in chronotherapy. 

In situ nasal absorption studies of midazolam were carried out in rats. The effects of solution concentration, osmolality, and pH on nasal absorption were studied using the in situ perfusion technique. The absorption of midazolam was reported to be prevented at osmolalities in the range of 142-450 mOsm/kg however, a hypoosmotic 3-mOsm/kg solution resulted in significant absorption, where the pH rose from 3.3 to 6.5. No lag time in absorption was observed when the solutions were buffered at a pH of either 5.5 or 7.4 however, at pH 3.3, no absorption was seen, suggesting... 

Additionally, since the stomach is one of the desired absorption sites for weakly acidic drugs, there should be no lag time in drug release from the GRDDS. Ideally, this type of delivery system is required for loop diuretics, such as furosemide and piretanide, in which the release of a certain amount of drug in the stomach is desired to obtain more balanced bioavailability. Consequently, this property prompted the development of floating systems for these acidic drugs. ... 

Metformin has an absolute oral bioavailability of about 50-60% of the dose after oral application of a single dose. Deconvolution analysis showed that after a short lag-time, the available remainder of the oral dose was absorbed at an exponential rate over about 6 h (Tucker et al., 1981). The bioavailability of phenformin seems to be more variable but also in the range of about 50% (Beckmann, 1968 Travis and Sayers, 1970). In general, absorption of biguanides is slower than their elimination, hence the plasma levels follow flip-flop kinetics (Pentikainen et al., 1979). 

Skin-snake-model percutaneous absorption Relationships between the in vitro permeability of basic compounds through shed-snake skin as a suitable model membrane for human stratum corneum and their physio-chemical properties were investigated. Compounds with low pKa values were selected to compare the permeabilities of the nonionized forms of the compounds. Steady-state penetration was achieved immediately without a lag time for all compounds. Flux rate and permeability coefficient were calculated from the steady-state penetration data and relationships between these parameters and the physico-chemical properties were investigated. The results showed that permeability may be controlled by the lipophilicity and the molecular size of the compounds. Equations were developed to predict the permeability from the MWs and the partition coefficients of basic compounds. 

A one-compartment model with first-order elimination was used to simulate unbound VPA concentrations. The two formulations differ only in the input function the ER formulation was accounted for through a zero-order input over 22 hours with 89% bioavailability. The DR formulation absorption was characterized by a 2h lag time (flag = 2h) followed by first-order absorption rate ka = 0.1 h ). The bioavailability F) of the DR preparation was assumed to be complete F = 1). 

Plot of Concentration-Time Profile for Population Data Set. It is advisable to plot the concentration-time profile of data for the entire population studied to reveal patterns and structure in the data (4) (see Chapter 14). Sometimes it might be necessary to drill into the plot of the profiles to examine different aspects of the profile. For instance, characterizing absorption may require examining the absorption phase of the concentration-time profile plot closely. This would enable the answering of questions such as Is there a lag time in absorption Is... 

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