P.J. Howard

Cimetidine and ranitidine increase midazolam bioavailability.

Cimetidine has been shown to inhibit the oxidative metabolism of a variety of low‐ and high‐extraction drugs. Despite the findings of initial investigators, there is evidence that ranitidine may exert similar effects. Eight healthy volunteer subjects took part in a within‐subject crossover study. They received midazolam, 15 mg, by mouth after pretreatment with cimetidine, ranitidine, or nothing and midazolam, 10 mg, intravenously on separate occasions. Mean absolute bioavailability of midazolam was increased by more than 30% after cimetidine (P < 0.01) and 26% after ranitidine (P < 0.05). The data, which agree with a concurrent clinical study indicating greater hypnotic action of midazolam after ranitidine, indicate that this is not a result of enhanced midazolam absorption and that reduced hepatic clearance is the most likely explanation.

A comparison between propofol and thiopentone as induction agents in obstetric anaesthesia

Two comparable series of 21 patients who had elective Caesarean section had general anaesthesia induced by thiopentone sodium 4.53 (SD 0.65) mg/kg or propofol 2.15 (SD 0.26) mg/kg. Maintenance was similar for both groups. Blood pressure was lower in the propofol group during the induction‐delivery interval. Umbilicallmaternal vein ratios for thiopentone and propofol were 8.5 and 7.2 respectively. Infant wellbeing as judged by Apgar score and cord blood analysis showed little difference between the two induction agents. Factors associated with uterine relaxation and bleeding were similar in the two groups.

A comparison of the early pharmacokinetics of midazolam in pregnant and nonpregnant women

The early pharmacokinetics of midazolam were compared in pregnant (active labour, awaiting and during elective Caesarean section) and matched gynaecological patients scheduled to undergo elective hysterectomy, half of whom were given an oxytocin infusion. A standard dose of 5 mg was given intravenously. For the first 15 minutes patients in labour had significantly higher plasma midazolam levels compared to all other groups. This was associated with the largest area under the curve (2 hours), the smallest volume of distribution and lowest clearance. Midazolam when given immediately before Caesarean section, can result in depression of the infant.

Plasma pentobarbitone levels.: Influence of the preparation, route and method of administration

In fit women plasma pentobarbitone was measured by gas-liquid chromatography after 100 mg given by mouth or intramuscular injection in the buttock using aqueous and organic solutions. Differences in plasma levels with the two solutions were not striking. Considerable inter-administrator difference occurred with significantly higher plasma levels when the drug was injected by a doctor using a 4 cm 21 s.w.g. needle as compared with nurses who used no specified injection technique. The oral route gave significantly higher plasma levels than nurse-given injections.

Effect of intravenous cimetidine on lignocaine disposition during extradural Caesarean section

We studied whether an intravenous bolus of cimetidine altered the disposition of extradurally administered lignocaine in the parturient. Mothers who requested extradural analgesia for elective Caesarean section were randomly pretreated with either cimetidine 200 mg intravenously (n = 5) or no H2‐receptor antagonist (n = 5). No difference was found between peak plasma lignocaine levels or area under the plasma concentration/time curve between the two groups after administration of 6 mg/kg lignocaine 2% with adrenaline 1:200 000. There was no evidence for an effect of a single intravenous dose of cimetidine on lignocaine disposition in the obstetric patient. In addition, the extradural administration of 6 mg/kg lignocaine produces plasma levels well below toxic levels.

Single dose oral H2-antagonists do not affect plasma lidocaine levels in the parturient

We studied whether a single oral dose of either cimetidine or ranitidine affects the disposition of epidurally administered lidocaine in the parturient. Patients given epidural analgesia for elective caesarean section were randomly pretreated with either cimetidine 400 mg (n=5), ranitidine 150 mg (n=7) or no H2 receptor antagonist (n=5). Following the administration of 400 mg of lidocaine 2% with adrenaline 1:200 000 no difference was found in peak plasma lidocaine levels or area under the plasma concentration/time curve (AUC) between the three groups. A single oral dose of cimetidine or ranitidine does not affect lidocaine disposition in the obstetric patient.