Search term

P h a r m a c o k i n e t i c s o f d i a z eeppa m a d m i n i s t e r e d i n t r a m uussc u l a r l y b y
a u t o i n j e c t o r ve r s u s re c t a l g e l i n h e a l t h y s u b j e c t s : a p h a s e I ,
r a n d o m i z e d , o p e n - l a b e l , ssiin g l e - d o s e , c r o s s o v e r, s i nnggl e - c e n t r e
s t u d y.
Lamson MJ, et al. Show all
Clin Drug Investig. 2011;31(8):585-97. doi: 10.2165/11590250-000000000-00000.
Pfizer Inc, Cary, NC, USA.
A
Abbssttrraacctt

BACKGROUND AND OBJECTIVE: Acute repetitive seizures (ARS) are a

debilitating part of episodic seizure activity that can sometimes progress to
status epilepticus. Currently approved treatment that can be administered by
non-medical personnel to patients with ARS is a diazepam rectal gel. While
effective, rectal administration can be difficult, inconvenient and objectionable. A
diazepam autoinjector has been developed to deliver diazepam via an
intramuscular (IM) injection. This study evaluated the dose proportionality of the
diazepam autoinjector and the consequent diazepam bioavailability relative to
an equivalent dose of diazepam administered rectally as a commercial gel.
METHODS: This was a phase I, randomized, open-label, two-part, single-dose,
crossover, single-centre pharmacokinetic study in 48 healthy young adult (aged
18-40 years) male and female subjects. Part I of the study (n=24) evaluated the
dose proportionality of three strengths of the diazepam autoinjector (5, 10 and
15 mg) administered into the mid-outer thigh via a deep IM injection. Part II (n=
24) assessed the relative bioavailability of the diazepam 10mg autoinjector
versus the diazepam 10mg rectal gel. Parts I and II were run concurrently. Each
subject completed screening up to 30 days prior to three (Part I) or two (Part II)
dosing periods. Serial blood sampling for plasma diazepam and
desmethyldiazepam (metabolite) concentrations, vital signs and adverse event
(AE) assessments were performed at prespecified times. Treatments were
separated by a 14-day washout period.
RESULTS: In Part I, dose proportionality was demonstrated for the diazepam
autoinjector at 5, 10 and 15 mg doses by increases in mean maximum plasma
concentration (C(max)), mean area under the plasma concentration-time curve
(AUC) from time zero to infinity (AUC()), and mean AUC from time zero to time
of last measurable concentration (AUC(last)). The median time to reach C(max)
(t(max)) was consistent at 1 hour for each dose. In Part II of the study, IM

administration via diazepam autoinjector (10 mg) resulted in plasma

concentrations of both diazepam and desmethyldiazepam that were slightly
higher and less variable than those observed following administration of
diazepam rectal gel (10 mg). The geometric mean ratio (diazepam
autoinjector/diazepam rectal gel) and 90% confidence intervals for diazepam
C(max) and AUC(last) were 0.94 (0.84, 1.05) and 1.14 (1.08, 1.21), respectively,
indicating that the overall bioavailability of the diazepam autoinjector was
approximately 14% higher than that of diazepam rectal gel. Both treatments were
generally well tolerated. Although the incidence of treatment-emergent AEs was
higher with diazepam autoinjector compared with diazepam rectal gel (21.7% vs
13.6%), the difference can be attributed to injection site pain. Injection site pain
also correlated with the diazepam autoinjector dose administered in Part I: 5 mg
(4.3%), 10 mg (21.7%) and 15 mg (27.3%). However, no patients discontinued the
trial due to injection site pain. No other AEs correlated with dose, and there was
no evidence of respiratory depression with either administration.
CONCLUSION: Results of the present study indicated that diazepam can be
safely and reliably administered IM using a diazepam autoinjector.
PMID 21721594 [PubMed - indexed for MEDLINE]
Full text: Springer

R
Reellaatteedd C
Ciittaattiioonnss

Show all

Bioavailability and dose proportionality of intramuscular diazepam administered by

autoinjector.
Diazepam autoinjector intramuscular delivery system versus diazepam rectal gel: A
pharmacokinetic comparison.
A phase I, randomized, open-label, crossover study of the single-dose pharmacokinetic
properties of guanfacine extended-release 1-, 2-, and 4-mg tablets in healthy adults.
Dose proportionality of fentanyl buccal tablet in doses ranging from 600 to 1300 microg
in healthy adult subjects: a randomized, open-label, four-period, crossover, single-centre
study.
Single-dose pharmacokinetics of once-daily cyclobenzaprine extended release 30 mg
versus cyclobenzaprine immediate release 10 mg three times daily in healthy young
adults : a randomized, open-label, two-period crossover, single-centre study.