Phenobarbital dosage

A man admitted to hospital on numerous oeeasions for pulmonary eompli-cations associated with cystic fibrosis, had average serum phenobarbital levels of 33 micrograms/mL while taking phenobarbital 200 mg daily and oral chloramphenicol 600 mg every 6 hours. One week after the antibacterial was withdrawn, his serum phenobarbital levels were 24 micrograms/mL even though the phenobarbital dosage was increased from 200 to 300 mg daily. ... 

An extremely well documented and well established interaction of clinical importance. The incidence seems to be high. The effects of concurrent use should be well monitored and suitable phenobarbital dosage reductions made as necessary to avoid toxicity. The dosage may need to be reduced by a third to a half. The significance of the modest reduction in valproate levels is not clear, especially as valproate levels do not correlate well with efficacy of treatment. Valproate has been associated with serious hepato-toxicity, especially in children aged less than 3 years, and this has been more common in those receiving other anticonvulsants. Valproate monotherapy is to be preferred in tbis group. 

The most common adverse reaction associated with phenobarbital is sedation, which can range from mild sleepiness or drowsiness to somnolence. These dru > may also cause nausea, vomiting, constipation, bradycardia, hypoventilation, skin rash, headache fever, and diarrhea Agitation, rather than sedation, may occur in some patients. Some of these adverse effects may be reduced or eliminated as therapy continues. Occasionally, a slight dosage reduction, without reducing the ability of the drug to control the seizures, will reduce or eliminate some of these adverse reactions. 

Detoxiflcation may be accomplished with phenobarbital (60 mg of phe-nobarbital for 500 mg of glutethimide). If concomitant codeine dependence is present (and this codependence should be strongly suspected), then methadone can be used adjunctively (10 mg of methadone for 120 mg of codeine) (Khajawall et al. 1982). Approximate sedative-hypnotic dosage equivalencies are listed in Table 3-5. 

Once seizures are terminated, dosages can be decreased by 1 mcg/kg/min every 2 hours. Successful discontinuation is enhanced by maintaining serum phenytoin concentrations above 20 mg/L and phenobarbital concentrations above 40 mg/L. 

Certain drugs induce the hepatic microsomal enzyme system i.e. enzyme induction, which decreases the effectiveness of other drugs, for example, if phenobarbital is suddenly discontinued without lowering the dosage of coumarin, severe hemorrhage can occur. 

The use of biodegradable polymers, especially polylactic acid (PLA), in oral solid dosage forms has been reported in the literature. PLA has been used as a matrix for phenobarbital tablets (9). Similarly, the use of polylactide as a matrix for oral dosage form of naproxen has also been reported (10). 

Other barbiturates are manufactured as a powder that is injected into the patient s vein. In addition, pentobarbital is manufactured as a suppository that is inserted in the rectum. Pentobarbital is also available in capsule, tablet, elixir, and injection dosages. Phenobarbital is produced in capsule, tablet, injection, and elixir dosages. 

Fusari and coworkers3 have developed a similar method for the assay of phenytoin and phenobarbital in dosage forms. They have used Silanized Celite 545 as the support material, 25% amyl alcohol in chloroform as the stationary phase and 0.05M borate buffer of pH 9.5 as the mobile phase. Phenobarbital was eluted with the mobile phase and phenytoin eluted with absolute ethanol. Ultraviolet absorption was used to quantitate the substances. 

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