Pregnant heroin-addicted women constitute a major social problem that should not be ignored. Newborns may develop a neonatal abstinence syndrome (NAS). They present with behavioural troubles running a typical clinical course. The level of severity of NAS will be accurately determined, leading to definition of the most appropriate therapy. The best therapeutic formula appears to be paregoric elixir, mixed with phenobarbital if necessary. Least severe cases can be easily controlled by appropriate surrounding conditions. Pharmacological as well as physiopathological effects of opiates are described. Little is known about the long-term effects of opiate exposure; they apparently include frequent instrumental troubles. At the present time, the rapid intervention of a multidisciplinary team is recommended, taking charge of the mothers who should receive methadone in progressively tapering doses.

The aim of the present study was to test the hypothesis that blockade of nociceptive input with bupivacaine during tonsillectomy can decrease pain beyond the immediate postoperative period. Fourteen patients between the ages of 6 and 18 years scheduled for tonsillectomy (with or without adenoidectomy) were randomly divided into two groups. The patients of both groups received 0.006 mg/kg atropine and anesthesia was induced by inhalation of halothane. Atracurium 0.5 mg/kg was used for myorelaxation. After oral intubation anesthesia was maintained with isoflurane plus nitrous oxide 67% in oxygen. In the bupivacaine group, 5 min before incision the tonsillar fossae were infiltrated with 0.25% bupivacaine with epinephrine (1 : 200,000). In the control group, the tonsillar fossae were infiltrated with normal saline with epinephrine (1 : 200,000). All patients received morphine 0.07 mg/kg (in the recovery room) and oral elixir with codeine 0.05 mg/kg plus acetaminophen 5 mg/kg every 4 h. Pain assessments were made using the visual analog (100 mm scale) self-rating method. Two types of pain were assessed: constant incisional pain and pain caused by drinking 100 ml of water. In the bupivacaine group, the constant pain score on the second day after surgery was 19 +/- 6 compared to 74 +/- 8 in the saline group (P less than 0.0002). By the 4-5th day after surgery almost no constant pain occurred in the bupivacaine group, but the pain score remained at the 40-60 level in the saline group. The difference in pain intensity on swallowing between the bupivacaine and saline groups was present even on the 10th postoperative day (1 +/- 1 vs. 14 +/- 5, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Steady-state plasma phenobarbital (PB) concentrations (n = 671) were measured in 438 inpatients. There was a significant relationship between age and PB dose ratio (concentration/dose or 1/clearance) for monotherapy patients; the dose ratio declined in the first year of life, but the dose ratio increased after age 1. The dose ratios were significantly higher in patients receiving PB in combination with other antiepileptic drugs. However, neither sex nor formulations used (tablet, elixir and intravenous) had any influence on the PB dose ratio. The age-dose-concentration relationships indicate that children, especially those under 11 years of age, may require maintenance PB doses more than 5 mg/kg/day to achieve the commonly recommended 'therapeutic' concentration range (10-40 mg/l).

Diarrhoeal diseases are the major cause of infant mortality in developing countries. Dehydration is the most common complication of diarrhoea, and severe dehydration causes up to 80% of diarrhoeal fatalities. For more than 100 years, physicians focused the treatment of diarrhoeal diseases on the symptom diarrhoea, and there were many 'antidiarrhoeal' drugs, such as water adsorbents (kaolin and pectin) and antiperistaltics (opium, paregoric elixir, diphenoxylate hydrochloride with atropine sulphate and loperamide). This approach focused on a non-dangerous symptom and diverted attention from the real killer, dehydration. A few decades ago, only severely dehydrated patients were treated by intravenous therapy. This treatment was prescribed by a group of professional health workers, administered intravenously by skilled nurses, and reserved for the few patients resident near health facilities. Oral rehydration therapy (ORT), developed 20 years ago, has several advantages over intravenous therapy; it can be administered at home, at health clinics or in modern hospitals, by parents or by nurses or physicians. Most serum disturbances in dehydrated neonates, infants, children, adults and the elderly are resolved by this treatment.

A reverse-phase high-performance liquid chromatographic method for the quantitation of phenobarbital and phenobarbital sodium in pharmaceutical dosage forms (elixir, injection, and tablets) was developed. The method is precise and accurate with percent relative standard deviations of 0.9 (without an internal standard) and 0.7 (with an internal standard) based on six injections. The method is stability indicating and is more sensitive than the revised USP-NF method. The products of decomposition showed two new peaks in the chromatogram.

A three-way crossover study was conducted with 24 healthy male volunteers to determine the relative bioavailability of four different 100-mg phenobarbital tablets compared with a reference elixir. Each subject received two of the tablets and the elixir at 30-d intervals. Blood samples were collected daily for 19 d after each dose. Plasma phenobarbital concentrations achieved with the five dosage forms differed by less than 20% within 2-3 h after dosing. The extent of absorption for all dosage forms, as determined from area under the plasma concentration-time profiles, were within 10% of each other. The peak plasma concentration was the greatest and the time to peak concentration was the shortest for the elixir. One of the tablets exhibited a time to peak concentration of 8.6 h, which was significantly longer than any of the other dosage forms. The time to peak concentration correlated with the percent of drug dissolved in 60 min, as determined in 0.1 M HCl, using the USP XX paddle method at 50 rpm.

Necrotizing enterocolitis developed in a premature infant after a medication in elixir form, calcium glubionate, was added to his feedings. The osmolalities of this medication and four others--theophylline elixir, phenobarbital elixir, dexamethasone elixir, and digoxin elixir--were measured by freezing-point depression and compared with the osmolalities of the analogous intravenous (IV) preparations. The osmolalities of the IV preparations were much lower than those of the corresponding oral preparations, except in the case of digoxin. When clinically appropriate doses of dexamethasone and phenobarbital elixirs were mixed in volumes of formula appropriate for a single feeding for a 1,500-g infant, the osmolalities of the drug-formula mixtures increased at least 300% over formula alone. This effect was less noticeable with digoxin elixir, theophylline elixir, and calcium glubionate.

A gas-liquid chromatographic (GLC) procedure has been developed for the assay and identification of amobarbital, butabarbital, heptabarbital, mephobarbital, pentobarbital, phenobarbital, and secobarbital in single component capsule, elixir, injectable, suppository, and tablet formulations. After extraction into chloroform from an acidified aqueous mixture of the product, the drug is eluted isothermally from a methylphenylsilicone GLC column at 210 or 240 degrees C and quantitated relative to thiamylal internal standard. Results were in good agreement with those obtained using pharmacopeial assay methods. The method is suitable for the rapid assessment of commercial formulations.

A high-performance liquid chromatographic separation is described for the analysis of phenobarbital in combination pharmaceutical dosage forms containing belladonna alkaloids. A mobile phase of 0.003 M tetramethylammonium chloride in water-methanol (3:2, pH 7.4) was used to separate phenobarbital from belladonna alkaloids on an octadecylsilane column in less than 7 min. The column effluent was monitored at 240 nm, which resulted in a detection limit of 6 ng of phenobarbital. The method is applicable to elixirs, tablets, and capsules with no preliminary extraction procedure. Data from the application of the method to commercial products is also presented.

Phenobarbital solubility in various binary and ternary propylene glycol-glycerol-water solvent systems was determined. Phenobarbital concentrations several times those of the ethanol-containing USP and BPC elixirs were obtained. From log solubility-solvent composition plots, a general equation was developed for phenobarbital solubility prediction in propylene glycol-water, glycerol-water, and propylene glycol-glycerol-water solvent systems. Solubility predictions using another equation, based on linear log solubility-dielectric constant relationships, were limited by the need to use different constants for different solvent blends. Heats of solution for phenobarbital determined in selected solvent blends as well as in USP and BPC elixirs varied within a very narrow range, suggesting similar solute-solvent interactions.

Theophylline bioavailability following chronic dosing of an elixir and two commercial tablet formulations (I and II) relative to an acute dose of elixir was evaluated in healthy volunteers. Both tablet formulations contained ephedrine. In addition, Tablet I contained hydroxyzine hydrochloride, and Tablet II contained phenobarbital. The mean area under the serum concentration-time curve (AUC) calculated either from time 0 leads to infinity for a single dose or over one dosing interval after repetitive doses was the highest after chronic administration of the elixir. The AUC after chronic elixir, in fact, was statistically different from the values after acute elixir (p less than 0.05) and Tablet II (p less than 0.05). There was, however, a large variation in the elimination half-life among the four theophylline treatments. The mean t 1/2 was the longest after chronic elixir followed by Tablet I, Tablet II, and acute elixir. The AUC values for the four treatments, when corrected for differences in t 1/2, were no longer significantly different, indicating that the extent of theophylline absorption was essentially the same from all three tested products. The time to peak and the peak serum concentration also did not differ among treatments. The prolongation in t 1/2 following chronic treatment with the elixir and its subsequent shortening during tablet administration suggest an initial inhibition followed by induction of theophylline metabolism. The changes may be due to the prolonged treatment with theophylline itself or the other drug ingredients in the dosage form.

The bioavailability of theophylline from single doses of an elixir (Elixophyllin) and two different tablet formulations, as compared to intravenous aminophylline, was studied with a crossover design in 12 normal volunteers. Both tablet formulations (Marax and Tedral) contain ephedrine. Marax contains hydroxyzine hydrochloride, and Tedral contains phenobarbital. The absorption of theophylline was most rapid from the elixir, whereas that from Marax was faster than that from Tedral. The peak concentrations of theophylline after administration of the 3 oral dosage forms were in the order, elixir greater than Marax greater than Tedral, however, the time to achieve peak concentration was highly variable and did not differ significantly among the 3 products. On the basis of area under the serum concentration-time curves, the absorption of theophylline from the elixir and from Marax was essentially complete. The area under the serum concentration curve after administration of Tedral was significantly less than that after intravenous aminophylline, elixir, and Marax; however, when the individual areas under the concentration curves were adjusted for intrasubject variation in elimination rate constant, the mean area under the concentration curve after Tedral no longer differed significantly from those of the intravenous and other two oral products. A large degree of intersubject variation in the oral absorption of theophylline was observe din this study. Therefore, in addition to the well-documented, large individual variation in the serum clearance of theophylline, intersubject differences in the absorption of the drug is another factor that complicates proper adjustment of the dose in oral theophylline therapy.