N. Barzaghi

Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects.

SummaryIdB 1016 is a complex of silybin (the main active component of silymarin) and phosphatidylcholine, which in animal models shows greater oral bioavailability and therefore greater pharmacological activity compared with pure silybin and silymarin. In order to assess its pharmacokinetic profile in man, plasma silybin levels were determined after administration of single oral doses of IdB 1016 and silymarin (equivalent to 360 mg silybin) to 9 healthy volunteers. Although absorption was rapid with both preparations, the bioavailability of IdB 1016 was much greater than that of silymarin, as indicated by higher plasma silybin levels at all sampling times after intake of the complex. Regardless of the preparation used, the terminal half-life was relatively short (generally less than 4 h). In a subsequent study, 9 healthy volunteers received IdB 1016 (120 mg b.i.d., expressed as silybin equivalents) for 8 consecutive days. The plasma silybin level profiles and kinetic parameters on day 1 were similar to those determined on day 8. Most of the silybin present in the systemic circulation was in conjugated form. Less than 3% of the administered dose was accounted for by urinary recovery of free plus conjugated silybin, a significant proportion of the dose probably being excreted in the bile. It is concluded that complexation with phosphatidylcholine in IdB 1016 greatly increases the oral bioavailability of silybin, probably by facilitating its passage across the gastrointestinal mucosa.

Pharmacokinetics of a valpromide isomer, valnoctamide, in healthy subjects

SummaryThe pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a prodrug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers.

Impaired Bioavailability of Famotidine Given Concurrently with a Potent Antacid

The effect of a high potency antacid on the oral bioavailability of a single dose of famotidine (40 mg) was evaluated in normal volunteers according to a randomized cross‐over design. Ingestion of the antacid concurrently with famotidine resulted in a significant reduction of peak plasma famotidine concentration (from 156 ± 22 to 104 ± 7, P < 0.05) and area under the famotidine plasma concentration curve (from 956 ± 125 to 607 ± 56, P < 0.02). No significant interaction was observed when the antacid was ingested 2 hours after famotidine administration.

Comparative pharmacokinetics and pharmacodynamics of eterobarbital and phenobarbital in normal volunteers

SummaryThe comparative pharmacokinetics and pharmacodynamics of single oral doses of eterobarbital (N, N′-dimethoxymethylphenobarbital, DMMP, 400 mg) and phenobarbital (200 mg) were evaluated in a double-blind study in 8 normal volunteers. Following administration of DMMP, no unchanged drug could be detected in serum. The active monomethoxymethyl metabolite (MMP) appeared rapidly in the circulation but its concentration remained generally low and declined below the limit of detection (0.5 μg/ml) usually before 9.5 h. Serum levels of DMMP-derived PB increased slowly and reached a peak between 24 and 48 h in most cases. One subject showed an atypical pharmacokinetic profile, characterized by relatively high levels of MMP and a delayed appearance of low levels of PB. After administration of PB, serum drug levels peaked within 1.5 h and remained, at all sampling times, higher than those observed after intake of DMMP. Compared with DMMP, PB induced greater sedative effects as assessed by visual analogue rating scale, critical flicker fusion frequency and multiple sleep latency tests.

Effects on cimetidine bioavailability of metoclopramide and antacids given two hours apart

SummaryPlasma cimetidine levels were determined in 9 normal subjects after a single oral dose of cimetidine 400 mg under control conditions, 2 h before metoclopramide 20 mg and 2 h after a potent antacid. The bioavailability of cimetidine was not significantly affected by metoclopramide and it was marginally reduced by the antacid.

Salicylic acid disposition in children with rheumatoid arthritis

Summary— The plasma level profile of SA and SUA after a single oral dose of ASA was studied in 8 children with juvenile rheumatoid arthritis, aged 3.5–15.0 years. Pharmacokinetic parameters were on average similar to those reported in the literature for adult subjects, although a somewhat larger intersubject variability was found.