Efficacy of Moxidectin 6-Month Injectable and ... - VetLearn.com

Document Sample
Efficacy of Moxidectin 6-Month Injectable and ... - VetLearn.com Powered By Docstoc
					                                                       D. D. Bowman, W. Legg, and D. G. Stansfield



Efficacy of Moxidectin 6-Month Injectable and
Milbemycin Oxime/Lufenuron Tablets Against
Naturally Acquired Toxocara canis Infections
in Dogs*
Dwight D. Bowman, MS, PhDa
Walter Legg, DVMb
David G. Stansfield, BVSc, MRCVSb
aCHK-R &D

17190 Polk Road
Stanwood, MI 49346
bNovartisAnimal Health
P.O. Box 26402
Greensboro, NC 27408




I ABSTRACT                                         I INTRODUCTION
   The efficacy of moxidectin injection (Pro-         Milbemycin oxime/lufenuron in a tablet for-
Heart® 6 Sustained Release Injectable for Dogs,    mulation (Sentinel® Flavor Tabs®, Novartis
Fort Dodge Animal Health) against naturally        Animal Health) to be given monthly is ap-
acquired infections of Toxocara canis was com-     proved for prevention of heartworm infections
pared with that of milbemycin oxime/               (Dirofilaria immitis), treatment and control of
lufenuron tablets (Sentinel® Flavor Tabs®, No-     intestinal infections with whipworms (Trichuris
vartis Animal Health). Eighteen dogs with nat-     vulpis) and ascarids (Toxocara canis and
urally acquired infections of T. canis were        Toxascaris leonina), and control of hookworms
ranked by egg counts and randomly assigned         (Ancylostoma caninum). Lufenuron, an insect
to treatment with moxidectin (170 µg/kg),          development inhibitor, has activity against flea
milbemycin (500 µg/kg)/lufenuron (10 mg/kg),       eggs produced by female fleas feeding on treat-
or to an untreated control group (six dogs per     ed dogs. The product is given monthly at a dose
treatment). Dogs were euthanized 7 days after      calculated to provide 500 µg milbemycin and
treatment for recovery, identification, and enu-   10 mg lufenuron/kg body weight.
meration of parasites by species. There was no        A commercial formulation of moxidectin
apparent efficacy for moxidectin against T. can-   (Proheart® 6 Sustained Release Injectable for
is. Conversely, milbemycin oxime/lufenuron         Dogs, Fort Dodge Animal Health) is admin-
was 91.5% effective against naturally occurring    istered to dogs for the prevention of canine
infections of this canine parasite.                heartworm infections and for the treatment
*Funding for this study was provided by Novartis   of existing larval and adult canine hookworm
Animal Health, Greensboro, North Carolina          infections (A. caninum and Uncinaria steno-


                                                                                              281
Veterinary Therapeutics • Vol. 3, No. 3, Fall 2002



cephla). The product is given by subcuta-            ment until necropsy. Housing, handling, and
neous injection every 6 months at a dose cal-        routine care conformed to standards estab-
culated to deliver 170 µg moxidectin/kg. Al-         lished at the facility. Each animal was identi-
though this injectable canine formulation            fied by a collar with an attached medallion
does not have a claim of efficacy against ca-        bearing a unique identification number, and
nine ascarids (T. canis and T. leonina), an in-      each cage was marked with the corresponding
jectable formulation of moxidectin designed          animal identification number. Except for the
for use in cattle (Cydectin® Injectable, Fort        day of dosing, dogs were provided nutritious,
Dodge Animal Health) has been shown to be            palatable food ad libitum throughout the day,
efficacious against T. canis when injected sub-      and food was removed in the evening for fast-
cutaneously to dogs at 200 µg moxidectin/kg          ing overnight. Water was available ad libitum.
body weight.1 Additionally, an oral paste for-
mulation of moxidectin (Quest®, Fort Dodge           Allocation and Treatments
Animal Health) is effective against several             Fecal samples were collected for fecal egg
species of equine parasites, including the large     counts on two occasions during the 7-day ac-
ascarid, Parascaris equorum.2                        climation period (treatment day = Day 0). A
   The present study examined the efficacy of        mean fecal egg (T. canis) count was calculated
moxidectin given by subcutaneous injection at        for each dog from these two samplings and
the dosage rate recommended for heartworm            dogs within each replicate were ranked by
and hookworm control in dogs against natu-           these egg counts and randomly allocated to
rally acquired adult T. canis infections. Efficacy   three groups of three dogs each. Treatments
of moxidectin was compared with that for a           (moxidectin injectable, milbemycin oxime/
group that received no treatment and a group         lufenuron, untreated control) were randomly
treated with milbemycin/lufenuron.                   allocated to each group thus formed.
                                                        Moxidectin was provided as the commercial-
I MATERIALS AND METHODS                              ly available injectable formulation designed for
Animals                                              heartworm prevention in dogs. The product
   Eighteen random-source adult dogs (15             was given according to label recommendations
males and three females) of various breeds, har-     at a dose that provided a minimum of 170 µg
boring patent, natural parasite infections (as       moxidectin/kg (Table 1). Milbemycin oxime/
determined by fecal flotation), were acquired        lufenuron combination also was obtained from
from sources that typically supply animals to        commercial sources and administered orally at
the research facility. Except for natural parasite   a dose calculated to deliver 500 µg milbemycin
infections, all dogs were determined to be           oxime and 10 mg lufenuron/kg body weight.
healthy by physical examination before dosing        The control groups did not receive any treat-
and were negative for heartworm microfilariae.       ment for parasites.
Because a sufficient number of naturally in-            Dogs of each replicate were individually
fected dogs could not be identified at one time,     weighed on their respective Day –1. On the
the study was performed in two replicate             morning of Day 0, a staff member experienced
groups of nine dogs, with three dogs per treat-      in injection techniques administered moxidectin
ment in each replicate.                              according to label instructions to dogs assigned
   In both replicates, dogs were individually        to that treatment. Dogs assigned to treatment
housed in cages or runs from the time of treat-      with milbemycin oxime/lufenuron were fasted


282
                                                            D. D. Bowman, W. Legg, and D. G. Stansfield



 TABLE 1. Dog Identification, Treatments, and Adult Toxocara canis Recovered
 at Necropsy
                       Mean
                    Pretreatment
 Treatment            T. canis                                                             T. canis
 Group              Egg Counts*    Dog ID       Sex      Weight (kg)        Dose          Recovered
 Control


                  {
                        293.5      10637        Male        28.4          Untreated          10
    Replicate 1          93.5      10593        Male        18.8          Untreated          13
                          9.5      10440        Male        31.0          Untreated           1

                        571.5      10672        Female      14.2          Untreated           6
    Replicate 2
                  {     190.0
                         56.5
                                   10670
                                   10749
                                                Female
                                                Male
                                                            13.7
                                                            26.7
                                                                          Untreated
                                                                          Untreated
                                                                                              7
                                                                                             15
 Geometric Grand Mean                                                                         7.1

 Moxidectin Injection
                    175.5          10646        Male        17.4          2.97mg             49
  Replicate 1
                  {  55.0
                     52.5
                                   34594
                                   10716
                                                Male
                                                Male
                                                            29.8
                                                            24.3
                                                                          5.09 mg
                                                                          4.17 mg
                                                                                             10
                                                                                              9

                      3450.0       10682        Female      11.5          1.98 mg            88
    Replicate 2
                  {     71.5
                        45.5
                                   10779
                                   10719
                                                Male
                                                Male
                                                            10.3
                                                            26.9
                                                                          1.78 mg
                                                                          4.48 mg
                                                                                              1
                                                                                              7
 Geometric Grand Mean (% Efficacy)                                                           13.1 (0%)

 Milbemycin Oxime/Lufenuron Tablets
                 270.0       10663              Male        18.5       26–50 lb tablet        2
  Replicate 1
                  {
                  52.5
                  36.0
                             10710
                             E2355
                                                Male
                                                Male
                                                            18.4
                                                            31.8
                                                                        26–50 lb tablet
                                                                       51–100 lb tablet
                                                                                              1
                                                                                              0

                        769.5      E2490        Male        35.9       51–100 lb tablet       0
    Replicate 2
                  {      89.0
                         13.5
                                   10628
                                   10715
                                                Male
                                                Male
                                                            19.1
                                                            18.8
                                                                        26–50 lb tablet
                                                                       26–50 lb tablet
                                                                                              2
                                                                                              0
 Geometric Grand Mean (% Efficacy)                                                            0.6 (91.5%)
 *Eggs per gram of feces.


overnight before dosing. On the morning of Day           ter dosing with milbemycin/lufenuron for evi-
0, whole milbemycin/lufenuron tablets hidden             dence of vomiting.
in food balls were administered orally by staff
members experienced in oral dosing techniques.           Necropsy and Parasite Counts
After dosing, dogs in this group were offered half          Seven days after treatment, all dogs in a
of their usual morning ration. All dogs were ob-         replicate were euthanized and the intestinal
served approximately every hour for 3 hours af-          tract was opened and thoroughly searched for


                                                                                                         283
Veterinary Therapeutics • Vol. 3, No. 3, Fall 2002



remaining T. canis using standard parasite re-       is present at necropsy. A mean of 0.8 worms
covery techniques. Contents from the lumen           was recovered from dogs in Replicate 1 and a
of the intestinal tract were washed through a        mean of 0.4 worms was recovered from this
40-mesh sieve, and all worms encountered             group in Replicate 2. The geometric grand
were recovered, enumerated, and identified ac-       mean T. canis remaining at necropsy after
cording to stage and species. Other parasite         treatment with milbemycin oxime/lufenuron
species were present in some dogs; however,          was 0.6 (91.5% efficacy).
counts are presented only for T. canis.
                                                     I DISCUSSION
Analysis                                                Moxidectin in the formulation and dosage
  Efficacy of the two treatments was based on        used for prevention of heartworm and hook-
the percent reduction for T. canis as compared       worm infection in dogs was ineffective against
with the worm count for the control group.           T. canis infections within 7 days after treat-
Parasite counts were transformed to the natural      ment in this study. In contrast, milbemycin
logarithm of (count + 1) for analysis and for        oxime/lufenuron was highly effective, remov-
calculation of geometric means. Efficacy of          ing more than 90% of the worms present. The
each treatment was calculated as follows:            lack of efficacy for moxidectin against this par-
                                                     asite species is possibly related to the adminis-
    Percent efficacy = ([Xc– X t]]/Xc) × 100
                                                     tration of the drug by the subcutaneous route.
where X c = geometric mean number of T. canis        The subcutaneous route of administration
recovered in the control group and X t = geo-        might possibly minimize the direct effect of the
metric mean number of T. canis recovered in          compound on the unattached worms within
the treatment group.                                 the intestine. Early work with milbemycin
                                                     oxime against T. canis has shown that the ma-
I RESULTS                                            jority of worms are shed within the first 2 days
   All dogs remained healthy and completed           after treatment and that all affected worms are
the study. No vomiting occurred in any dog af-       passed within 5 days after treatment.3 Howev-
ter oral administration of milbemycin oxime/         er, no information was found on the rate of
lufenuron tablets. A mean of 5.8 T. canis was        worm kill with the administration of mox-
recovered from the control group in Replicate        idectin. Thus, it is conceivable that the phar-
1 and a mean of 8.6 T. canis was recovered           macokinetics of the injectable moxidectin for-
from controls in Replicate 2. The grand mean         mulation could provide for achievement of
number of T. canis recovered from the control        peak levels in the intestines several days after
group was 7.1 (Table 1).                             treatment. If this does occur, a higher rate of
   All dogs treated with moxidectin injection        efficacy might have been observed by perform-
had T. canis present at necropsy. A mean of          ing necropsies on dogs treated with injectable
16.7 was recovered from dogs in Replicate 1          moxidectin 3 to 7 days later than they were
and a mean of 10.3 was recovered from dogs           done in this study.
in Replicate 2. The geometric grand mean                Currently, milbemycin oxime is available in
T. canis recovered from dogs treated with mox-       two formulations for prevention of canine heart-
idectin was 13.1 (0% efficacy).                      worm disease (Interceptor® and Sentinel® Flavor
   Only three of the six dogs treated with           Tabs®). In addition to heartworm prevention,
milbemycin oxime/lufenuron had live T. can-          both milbemycin formulations are effective


284
                                                        D. D. Bowman, W. Legg, and D. G. Stansfield



against canine ascarids and whipworms and pro-      canine ascarid, T. canis. Additionally, this com-
vide control of canine hookworms. The latter of     bination provides excellent efficacy against T.
the two formulations also contains lufenuron,       vulpis and A. caninum infections in dogs.
which provides control of flea populations by in-
hibition of egg development.
                                                    I REFERENCES
                                                     1. Martinez-Labat P, Garrido-Alcala Y, Vizzuett-Re-
I CONCLUSION                                            sendiz B: Prueba critica a la moxidectina como anti-
   Moxidectin, given by injection at the dosage         nematodico alternativo en caninos. Vet Argentina 13:
                                                        520–525, 1996.
recommended for control of canine heartworms
                                                     2. Costa AJ, Barbosa OF, Moraes FR, et al: Comparative
and hookworms, had virtually no effect on the           efficacy evaluation of moxidectin gel and ivermectin
number of adult T. canis in this study. In con-         paste against internal parasites of equines in Brazil. Vet
trast, milbemycin oxime/lufenuron, given orally         Parasitol 80:29–36, 1998.
                                                     3. Bowman DD, Parsons JC, Grieve RB, et al: Effects of
at the dosage rate recommended for control of
                                                        milbemycin on adult Toxocara canis in dogs with ex-
heartworm and certain intestinal parasites of           perimentally induced infection. Am J Vet Res 49:
dogs, demonstrated excellent efficacy against the       1986–1989, 1988.




                                                                                                            285

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:2
posted:2/9/2013
language:English
pages:5