Plasma levels, drugs after application

Orally administered psoralens are rapidly absorbed (maximum photosensitivity for the most common preparation, 8-methoxypsoralen [Oxsoralen Ultra], is 1-1.5 hours). Although the elimination half-life is 2.2 hours, the skin remains photosensitive for 8 to 12 hours. Most excretion is renal, and the drug does not accumulate. It can be absorbed if applied topically, and after application to the entire body, therapeutic plasma levels can be detected. 

Accordingly, the metabolic stability of BP 2.94 in vivo was strikingly enhanced as compared to the active drug. Following oral application of BP 2.94 (36) to healthy human volunteers, the progressive hydrolysis of the prodrug led to a parallel decrease in plasma levels of both compounds. A plasma half-life of 1 h was obtained for liberated (/ )-a-methylhistamine (12) and > 24 h for BP 2.94 (36) as compared to 3 min for non-derivatized (7 )-a-methylhistamine (12). The bioavailability in healthy human volunteers expressed as area under the curve (AUC) of (/ )-a-methylhistamine (12) was about 100-fold increased after oral application of BP 2.94 (36) at a dose of... 

Plasma concentration profiles after buccal administration of the saturated drug solution varied considerably between animals but the overall time dependency was similar (Figure 4). Plasma levels increased rapidly after application of the solution onto the mucosa to produce relatively constant concentrations in the range 1500-8000 ng/ml after 2 h. Following removal of the solution the drug exhibited the expected decline in plasma concentrations at a rate comparable to that observed in the intravenous bolus study. 

Plasma concentrations of diclofenac sodium after application of the transbuccal delivery device (Figure 6) followed a different time course to that observed with the saturated solution. Plasma concentrations of the drug increased rapidly over the initial phase and achieved peak values of 2400-4000 ng/ml at 1 h after system application. Thereafter, the levels decreased slowly and converged to a mean value of 2250 ng/ml before the system was removed. Based on depletion analysis, 7.8 mg was delivered on average from the hydrogel discs over 4 h. 

Mast cell stabilizers are relatively safe drugs to use.This is likely the result of minimal ocular or systemic absorption after topical application to the eye. Adverse reactions far mast cell stabilizers are rare but may include stinging or burning most commonly, with less common presentations that include conjimctival injection and itchy and watery eyes. Systemically, there is a low potential far adverse reactions because of the low plasma levels of the drug. Headache, however, is a common adverse effect, particularly for nedocromil and pemirolast. Other adverse reactions, along with a delineation of specific drug and side effects, are listed in Table 13-6. 

Ho and collaborators [68] injected 10,000 U/m2 i.m. or 16,500-100,000 U/m2 i.v. of E. coli 1-ASP into adults with metastatic cancer or leukemia. A plateau in plasma after i.m. injection was not reached until 14-24 hours after drug administration. The peak plasma level was 1.12 U/mL, about one fourth of the activity reached when the same dose was given i.v. The in vivo half-life was 46 hours (after i.m. application) compared to 7-28 hours for the i.v.-administered drug. The volume of distribution after i.m. administration was four times that after i.v. administration. Consequently, the area under the curve after i.m. administration was only 1/24 that by i.v. route. 

The drug is metabolized rapidly in the liver, kidney, intestinal mucosa, and even red blood cells. Therefore it has a plasma half-life of only 10 min after bolus intravenous application. The major metabolite, uracil arabinoside (ara-U), can be detected in the blood shortly after cytarabine administration. About 80% of the dose is excreted in the urine within 24 h, with less than 10% appearing as cytarabine the remainder is ara-U. After continuous infusion, cytarabine levels in the liquor (cerebro-spinal fluid) approach 40% of that in plasma. Continuous infusion schedules allow maximal efficiency, with uptake peaks of 5-7 pM. It can be administered intrathecally as an alternative to methotrexate. 

CGP 57813 is a peptidomimetic inhibitor of human HIV-1 protease. This lipophilic compound has been successfully entrapped in polylactic acid (PLA) and into pH-sensitive methacrylic acid copolymer particles (EUDRAGIT L 1 GO-55) [69], After the application of a film-coating, the plasma concentration was acceptable and reached similar levels as with injections of drug-loaded PLA carriers. To hinder the proteolytic degradation of a drug, two types of enteric-coated pellets were applied simultaneously. One contained the protease inhibitor coated... 

Prolonged-release (or slow-release) preparations are useful for water-soluble drugs with short biological half-lives. Hydrophobic CyDs, such as ethylated CyDs, with low aqueous solubilities have been demonstrated to work as slow-release carriers of water-soluble drugs such as isosorbide dinitrate, diltiazem hydrochloride, and 5-fluorouracil [19, 38, 39]. For example, 15 has the most prominent retarding effect for water-soluble molsidomine and diltiazem hydrochloride, after oral administration in dogs. The release of isosorbide dinitrate from 16 film was retarded and the plasma drug level after topical application of the film to rat abdominal skin was maintained at 100 ng mL for about 10 h [41]. 

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