Erratic absorption

HYDANTOINS Fhenytoin is the most commonly prescribed anticonvulsant because of its effectiveness and relatively low toxicity. However, a genetically linked inability to metabolize phenytoin has been identified. For this reason, it is important to monitor serum concentrations of the drug on a regular basis to detect signs of toxicity Fhenytoin is administered orally and parenterally. If the drug is administered parenterally, the IV route is preferred over the intramuscular route because erratic absorption of phenytoin causes pain and muscle damage at the injection site... 

In patients who have failed initial therapy (i.e., salvage), liposomal amphotericin products, itraconazole, or the echinocandin caspofungin can be used. Itraconazole has a response rate of approximately 40%.100 Oral itraconazole exhibits erratic absorption the IV formulation is suspended in cyclodextrin, which is eliminated renally, and thus IV itraconazole should be avoided in patients with a creatinine clearance of less than 30 mL/minute (0.29 mL/s m2).103 Itraconazole also has negative inotropic cardiac effects and increases the serum concentrations of medications (e.g., cyclophosphamide, etopo-side, calcineurin inhibitors, and sirolimus). 

Above 5 Low solubility and poor oral bioavailability. Erratic absorption. High metabolic liability, although potency may still be high. Basic amines tend to show high to very high Vd (Volume of distribution = ratio of overall tissue binding to plasma protein binding)... 

Bretylium (L) showed selective adrenergic blocking activity in animals and man but erratic absorption and other side effects limited its utility in hypertension (61). 

Route of administration alters the effectiveness of cannabinoids. Orally administered THC has a slower and more erratic absorption. THC was found to be 45 times more effective for analgesia after intravenous than after subcutaneous administration (Martin 1985). The pharmacokinetics of different chemical constituents of cannabis vary (Consroe et al. 1991). The elimination half-life of cannabidiol is estimated to be about 2-5 days, with no differences between genders. Comparably, the elimination half-life of Al-THC is approximately 4 days, and may be prolonged in chronic users (Johansson et al. 1988, 1989). 

Corbamazepine is slowly absorbed and tends to exhibit erratic absorption following oral administration. Hence, when dispensing repeat prescriptions for corbamazepine, it is advisable to avoid changing the formulation of corbamazepine. 

Rectal Avoids problems of stability in gastrointestinal tract No first-pass metabolism Useful if oral administration is not possible Unpopular Inconvenient Erratic absorption Irritation Suppositories, enemas (solutions, suspensions, emulsions), foams, ointments, creams... 

Vaginal Local or systemic effects (hormones) No first-pass metabolism Inconvenient Erratic absorption Irritation Creams, ointments, foams, tablets, pessaries... 

Absorption/Distrlbutlon - Phenytoin is slowly absorbed from the small intestine. Rate and extent of absorption varies and is dependent on the product formulation. Bioavailability may differ among products of different manufacturers. Administration IM results in precipitation of phenytoin at the injection site, resulting in slow and erratic absorption, which may continue for up to 5 days or more. Plasma protein binding is 87% to 93% and is lower in uremic patients and neonates. Volume of distribution averages 0.6 L/kg. Phenytoin s therapeutic plasma concentration is 10 to 20 mcg/mL, although many patients achieve complete seizure control at lower serum concentrations. 

Phenytoin (Dilantin) [Anticenvulsant/Hydantoin] Uses Sz disorders Action X Sz spread in the motor cortex Dose Load Adults Peds. 15-20 mg/kg IV, 25 mg/min max or PO in 400-mg doses at 4-h intervals Maint Adults. Initial, 200 mg PO or IV bid or 300 mg hs then follow levels Peds. 4-7 mg/kg/24h PO or IV -s- daily-bid avoid PO susp (erratic absorption) Caution [D, +] Contra Heart block, sinus bradycardia Disp Caps, susp, inj SE Nystag-mus/ataxia early signs of tox gum hyperplasia w/ long-term use. IV BP, bradycardia, arrhythmias, phlebitis peripheral neuropathy, rash, blood dyscrasias, Stevens-Johnson synd Notes Levels Trough Just before next dose Therapeutic Peak 10-20 mcg/mL Toxic >20 mcg/mL phenytoin albumin bound, levels = bound free phenytoin w/ i albumin azotemia, low levels may be therapeutic (nl free levels) Interactions T Effects W/ amiodarone, allopurinol, chloramphenicol, disulfiram, INH, omeprazole, sulfonamides, quinolones, trimethoprim t... 

Mechanism of Action A phenothiazine that antagonizes dopamine neurotransmission at synapses by blocking postsynaptic dopaminergic receptors in the brain. Therapeutic Effect Decreases psychotic behavior. Also produces weak anticholinergic, sedative, and antiemetic effects and strong extrapyramidal effects. Pharmacokinetics Erratic absorption. Protein binding greater than 90%. Metabolized in liver. Excreted in urine. Half-life 33 hr. 

Despite the problems posed by the pharmacokinetic and physicochemical characteristics of ibuprofen (small therapeutic window, erratic absorption owing to its poor solubility, etc.), this pulsed release system results in good separation of the two plasma peaks (indicating that there is in fact delayed release of the second drug dose) at the desired concentrations. 

Erratic absorption of soft gelatin capsules and oral solution necessitates 2 Si. repeated monitoring of cyclosporine blood levels... 

Sandimmune is the original formulation of cyclosporine used in clinical transplantation. Erratic absorption of the formulation has limited its use in transplant recipients. Many long-term transplant recipients continue on Sandimmune . The formulation has been supplanted by the micro-emulsion formula of cyclosporine. 

Oral Easy, safe, convenient Limited or erratic absorption of some drugs chance of first-pass inactivation in liver Analgesics sedative-hypnotics many others... 

The medical use of opium as a pain-relieving drug dates back to the third century. Arab physicians used extracts of the oriental poppy to treat diarrhoea and probably introduced it to the Far East. However, because of its erratic absorption from the gastrointestinal tract, its use as an effective analgesic only became possible with the introduction of the hypodermic syringe in the middle of the last century. 

Disadvantages are poor absorption in peripheral circulatory failure. Repeated injections at one site can cause lipoatrophy, resulting in erratic absorption (see Insulin). 

Griseofulvin has extremely low aqueous solubility, and material of normal particle size gave rise to poor and erratic absorption. Microsize particles improve absorption, but it is improved even more when it is formulated in ultramicrosize particles as a monomolecular dispersion in polyethylene glycol. 

Oral (PO) Absorption may vary Generally slower absorption rate compared to IV bolus or IM injection Safest and easiest route of drug administration May use immediate-release and modified-release drug products Some drugs may have erratic absorption, be unstable in the gastointestinal tract, or be metabolized by liver prior to systemic absorption... 

Ketoconazole is water-soluble at a pH of below 3. Its oral absorption is influenced by the acidity of the stomach contents, and the concomitant administration of histamine H2 receptor antagonists, proton pump inhibitors, antacids, or food affects its absorption. A high carbohydrate meal ingested with ketoconazole reduces total drug absorption, while a high lipid meal increases it. Erratic absorption is particularly apparent in patients with AIDS. Peak serum concentrations are seen within 2-3 hours. The half-life is about 8 hours. CSF penetration is less than 10% (1). Ketoconazole is extensively metabolized in the liver and excreted in the bile in an inactive form less than 1% of the active drug is excreted in the urine. Clearance is not significantly altered by renal dialysis (1). 

Halofantrine, a highly lipophilic antimalarial drug with poor and erratic absorption, is metabolized to its equi-potent metabolite desbutylhalofantrine and this is inhibited by oral ketoconazole (41). 

In the USA, cisapride was only available as an oral formulation, which was poorly absorbed when given by intragastric administration (Steel et al 1998) or per rectum (Cook et al 1997, Steel et al 1999). The use of cisapride in horses has been limited by the erratic absorption of the drug from... 

The balance between medicinal use of a drug and the abuse potential is a delicate balance. One of the main points brought by the medicinal marijuana proponents is the fact that the currently available soft gelatin capsule formulation is very expensive and lacks consistency in its effects. The latter point could be explained based on the fact that oral THC has erratic absorption from the gastrointestinal tract, is subject to the first-pass effect resulting in heavy metabolism with production of high levels of 11-OH-THC, and undesirable side effects. 

---